Ipou/abnormal chemosensory jump 6


As a POU domain transcription factor, Ipou is related to an evolutionary complex group of genes consisting of at least 5 classes. Pit-1 is a class I POU domain transcription factor involved in the development of the anterior pituitary gland in mammals. Class II POU domain transcription factors include mammalian Oct1, Oct2, Oct11 and Drosophila PDM-1 and PDM-2. Mammalian Brn1, Brn2, Brn4, SCIP/Oct6 and Xenopus XLPOU1 and XLPOU2 and well as Drosophila Ventral veins lacking (Drifter/Cf1a) and C. elegans ceh6 are Class III proteins. Ipou is in POU domain group IV, along with C. elegans unc86 and vertebrate Brn3. Oct-3/4 is a class V POU domain protein. There is no known Drosophila class 1 or class V homolog (Verrijzer, 1993).

C. elegans POU domain homolog unc-86

The POU homeo box gene unc-86 specifies neuroblast and neural identities in the developing C. elegans nervous system. After an asymmetric neuroblast division, unc-86 is expressed in one of two daughter cells in 27 lineage classes that are not obviously related by either function or position. unc-86 transcriptional regulatory regions detect cell lineage asymmetry to activate unc-86 expression in one of two neuroblast daughter cells. Distinct regulatory regions activate unc-86 expression in particular sets of sublineages. Therefore the unc-86 regulatory region integrates distinct cell lineage asymmetry cues to activate unc-86 expression in the many classes of neuroblast cell lineages. In agreement with such lineage-specific regulation of unc-86 asymmetric activation, mutations in lin-11 (LIM homeo box), ham-1, and lin-17 affect the asymmetry of unc-86 expression in particular cell lineages, and mutations in lin-32 (achaete/scute family), vab-3 (Pax-6 homolog) and egl-5 (Abd-B homolog) affect the establishment of unc-86 expression in other cell lineages. Homologs of unc-86 as well as many of these unc-86 regulators have been implicated in control of neurogenesis in both vertebrates and invertebrates. These data suggest that unc-86 acts in a phylogenetically conserved pathway that couples neuroblast cell lineage asymmetry to the generation of diverse neural types (Baumeister, 1996).

Genes regulated by unc-86 are mostly unknown. A genetic strategy was devised for the identification of downstream pathways regulated by unc-86. UNC-86 transcription activity was activated by inserting the VP16 activation domain into an unc-86 genomic clone that bears all regulatory sequences necessary for normal expression in C. elegans. unc-86/VP16 complements unc-86 mutations in the specification of neuroblast and neural cell fates, but displays novel genetic activities: it can suppress non-null mutations in the downstream genes mec-3 (a LIM-homeobox gene and homolog of Drosophila Islet) and mec-7 (coding for a mecanosensory neuron-specific ß-tubulin) that are both necessary for mechanosensory neuron differentiation and function. Note: for additional information on tubulin functions, see ß1 tubulin. These data suggest that UNC-86/VP16 increases the expression of mec-3 and mec-7 to compensate for the decreased activities of mutant MEC-3 or MEC-7 proteins. The suppression of mutations in downstream genes by an activated upstream transcription factor should be a general strategy for the identification of genes in transcriptional cascades. unc-86/VP16 also causes neural migration and pathfinding defects and novel behavioral defects. Thus, increased or unregulated expression of genes downstream of unc-86 can confer novel neural phenotypes suggestive of roles for unc-86-regulated genes in neural pathfinding and function. Genetic suppression of these unc-86/VP16 phenotypes may identify the unc-86 downstream genes that mediate these events in neurogenesis (Sze, 1997).

While UNC-86 alone is able to activate transcription of the mec-3 promoter in vitro, the LIM homeodomain protein (MEC-3) fails to bind DNA or activate transcription on its own. However, in the presence of both UNC-86 and MEC-3, there is cooperative binding to the mec-3 promoter and synergistic activation of transcription in vitro. Protein-protein interaction assays reveal that UNC-86 can bind directly to MEC-3: in vitro transcription studies indicate that both proteins contain a functional activation domain. Thus, formation of a heteromeric complex containing two activation domains results in a highly potent activator (Lichtsteiner, 1995)

UNC-86 and the LIM-type homeodomain protein MEC-3 bind cooperatively as a heterodimer to the mec-3 promoter. This heterodimer formation increases DNA binding stability and, therefore, increases DNA binding specificity. The in vivo significance of this heterodimer formation in neuronal differentiation is suggested by (1) a loss-of-function mec-3 mutation whose product in vitro binds DNA well but forms heterodimers with UNC-86 poorly and (2) a mec-3 mutation with wild-type function whose product binds DNA poorly but forms heterodimers well (Xue, 1993).

To better understand the diversity of function within the POU domain class of transcriptional regulators, the optimal DNA recognition site for several proteins of the POU-IV (Brn-3) subclass was determined by random oligonucleotide selection. The consensus recognition element derived in this study, ATAATTAAT, is clearly distinct from octamer sites described for the POU factor Oct-1. The optimal POU-IV site determined here also binds Brn-3.0 with significantly higher affinity than consensus recognition sites previously proposed for this POU subclass. The binding affinity of Brn-3.0 on its optimal site, on several variants of this site, and on several naturally occurring POU recognition elements is highly correlated with the activation of reporter gene expression by Brn-3.0 in transfection assays. The preferred DNA recognition site of Brn-3.0 resembles strongly the optimal sites of another mammalian POU-IV class protein, Brn-3.2, and of the Caenorhabditis elegans Brn-3.0 homolog Unc-86, demonstrating that the site-specific DNA recognition properties of these factors are highly conserved between widely divergent species (Gruber, 1997).

The C. elegans hermaphrodite nervous system is composed of 302 neurons that fall into at least 118 diverse classes. cfi-1 contributes to the development of neuronal diversity. cfi-1 promotes appropriate differentiation of the URA sensory neurons and inhibits URA from expressing the male-specific CEM neuronal fate. The UNC-86 POU homeodomain protein is present in CEM and URA neurons, and can promote expression of CEM-specific genes in both CEM and URA, but CFI-1 inhibits expression of these genes in the URA cells. cfi-1 also promotes appropriate differentiation and glutamate receptor expression in the AVD and PVC interneurons. cfi-1 encodes a conserved neuron- and muscle-restricted DNA-binding protein containing an A/T rich interaction domain (ARID). In the eARID, CFI-1 is 70%, 73%, and 72% identical to the Drosophila Dead ringer protein, and the mammalian Dril1 (Bright) and Dril2 proteins, respectively. These proteins share other regions of similarity with CFI-1 as well, suggesting that they are orthologs. ARID proteins regulate early patterning and muscle fate in Drosophila, but they have not previously been implicated in the control of neuronal subtype identity (Shaham, 2002).

Transcriptional regulators play important roles in creating diversity in the nervous system. The most well-understood cell fate regulators are the families of homeodomain proteins. The POU homeodomain proteins, including C. elegans UNC-86, affect development of many neurons; the Pax homeodomain proteins subdivide the vertebrate neural tube into distinct domains; and the LIM-homeodomain proteins generate a variety of motor neurons in the vertebrate spinal cord and contribute to the diversity of sensory neurons and interneurons in C. elegans. Homeodomain proteins typically function in a context that is defined by other DNA-binding proteins. In the URA and IL2 neurons, CFI-1 represents an important factor that modifies the activity of UNC-86 to match a particular cell type (Shaham, 2002).

unc-86 is essential for the development of the URA and IL2 neurons, where it induces expression of cfi-1. cfi-1, in turn, activates normal URA and IL2 gene expression and prevents inappropriate expression of CEM-specific genes. If cfi-1 is absent from URA and IL2 neurons, unc-86 promotes expression of the CEM-specific marker pkd-2::GFP instead, as it would normally do in CEM neurons. These results indicate that during normal development a cfi-1-dependent activity prevents unc-86-dependent induction of CEM-specific genes in URA and IL2 neurons. Such a cfi-1-dependent activity could function by qualitatively changing UNC-86 from an activator of gene expression to a repressor. Alternatively, a cfi-1-dependent activity could prevent the association of UNC-86 or an UNC-86 target protein with regulatory regions of CEM-specific genes. In either model, the absence of CFI-1 function in CEM neurons would allow UNC-86 to activate pkd-2 in these cells (Shaham, 2002).

A fundamental question in developmental neurobiology is how a common neurotransmitter is specified in different neuronal types. Cell-specific regulation of the serotonergic phenotype by the C. elegans POU-transcription factor UNC-86 is described. unc-86 regulates particular aspects of the terminal neuronal identity in four classes of serotonergic neurons, but the development of the ADF serotonergic neurons is regulated by an UNC-86-independent program. In the NSM neurons, the role of unc-86 is confined in late differentiation: the neurons are generated but do not express genes necessary for serotonergic neurotransmission. unc-86-null mutations affect the expression in NSM of tph-1, which encodes the serotonin synthetic enzyme tryptophan hydroxylase, and cat-1, which encodes a vesicular transporter that loads serotonin into synaptic vesicles, suggesting that unc-86 coordinately regulates serotonin synthesis and packaging. However, unc-86-null mutations do not impair the ability of NSM to reuptake serotonin released from the ADF serotonergic chemosensory neurons and this serotonin reuptake is sensitive to the serotonin reuptake block drugs imipramine and fluoxetine, demonstrating that serotonin synthesis and reuptake are regulated by distinct factors. The NSM neurons in unc-86-null mutants also display abnormal neurite outgrowth, suggesting a role of unc-86 in regulating this process as well (Sze, 2002).

The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types

Transcription factors that drive neuron type-specific terminal differentiation programs in the developing nervous system are often expressed in several distinct neuronal cell types, but to what extent they have similar or distinct activities in individual neuronal cell types is generally not well explored. This problem was investigated using, as a starting point, the C. elegans LIM homeodomain transcription factor ttx-3, which acts as a terminal selector to drive the terminal differentiation program of the cholinergic AIY interneuron class. Using a panel of different terminal differentiation markers, including neurotransmitter synthesizing enzymes, neurotransmitter receptors and neuropeptides, it was shown that ttx-3 also controls the terminal differentiation program of two additional, distinct neuron types, namely the cholinergic AIA interneurons and the serotonergic NSM neurons. The type of differentiation program that is controlled by ttx-3 in different neuron types is specified by a distinct set of collaborating transcription factors. One of the collaborating transcription factors is the POU homeobox gene unc-86, which collaborates with ttx-3 to determine the identity of the serotonergic NSM neurons. unc-86 in turn operates independently of ttx-3 in the anterior ganglion where it collaborates with the ARID-type transcription factor cfi-1 to determine the cholinergic identity of the IL2 sensory and URA motor neurons. In conclusion, transcription factors operate as terminal selectors in distinct combinations in different neuron types, defining neuron type-specific identity features (Zhang, 2014).

Xenopus Brn3 homologs

The basic helix-loop-helix (bHLH) factor Xath5 promotes retinal ganglion cell differentiation when overexpressed and may do so by regulating the expression of factors involved in the differentiation of these cells. Potential candidates include the Brn3 POU-homeodomain transcription factors, which have been implicated in retinal ganglion cell development. A new member of the Brn3 gene subfamily in Xenopus, XBrn3d, has been identified. In situ hybridization analysis shows XBrn3d expression in developing sensory neurons and developing ganglion cells of the retina. Using a hormone-inducible Xath5 fusion protein, it has been shown that in animal caps Xath5 can directly regulate the expression of XBrn3d. Since XBrn3d is also expressed in sensory populations where Xath5 is not expressed, the regulation of XBrn3d expression by the bHLH factor XNeuroD was examined. A XNeuroD-hGR fusion protein is similarly able to directly induce the expression of XBrn3d in animal caps. In addition, overexpression of XBrn3d by RNA injection promotes the expression of ectopic sensory neuronal markers in the lateral ectoderm, suggesting a role in regulating neuronal development. Therefore, Xath5 and XNeuroD can directly regulate the expression of a neuronal subtype-specific factor, providing a link between neuronal differentiation and cell fate specification (Hutcheson, 2001).

The earliest XBrn3d expression is observed at stage 16 in two stripes within the neural plate and in the presumptive trigeminal placodes in the anterior portion of the embryo. At early tailbud stages (stage 26-31), XBrn3d is expressed in the spinal cord, the optic vesicle, the olfactory placode, the optic tectum, and a number of cranial ganglia. These include the trigeminal (cgV), facial (cgVII), glossopharyngeal (cg IX), and vagal (cg X) ganglia. Staining is maintained in the optic tectum, cgV, and the otic vesicle through stage 40. By stage 36, however, expression in the other ganglia and spinal cord has disappeared. Within the neural tube, staining encompasses the entire dorsal half in the region of the developing optic tectum and is also found in the dorsal-most portion of the spinal cord. Expression of XBrn3d in the neural retina is first detectable in whole mounts at stage 26-27 and by stage 29 XBrn3d was strongly expressed in the eye. Sectioned retinas at stage 34 and stage 41 show that XBrn3d is expressed throughout the retinal ganglion cell layer and into the ciliary marginal zone (CMZ), but is absent from the inner nuclear and outer nuclear layers. The CMZ is a region of ongoing neurogenesis at the peripheral margins of the Xenopus retina. Within the CMZ there is a peripheral to central gradient of retinal cell differentiation with undifferentiated stem cells located most peripherally and differentiating progenitors more centrally located. This is reflected by sequential activation of gene expression from the peripheral to the central region of the CMZ. Within the CMZ, XBrn3d expression is widespread in the more central region, which corresponds to postmitotic neurons that have just been born and are beginning to differentiate. In the central retina, where the retinal neurons are fully differentiated, XBrn3d expression is restricted to the retinal ganglion cell layer. The pattern of XBrn3d expression is reminiscent of that of mBrn3b, suggesting a role as an important differentiation factor for retinal ganglion cells in the developing frog retina (Hutcheson, 2001).

XBrn3d is able to promote the expression of ectopic sensory neuronal markers. The mechanism by which it has these effects is unclear. The loss of Rohon-Beard cells seen during neural plate stages suggests that XBrn3d is not promoting sensory development by directing ectoderm or other tissues to switch fates in a classic proneural sense. Additional explanations in which overexpression of XBrn3d has no direct effect on the specification of sensory neurons are possible. For instance, the overexpression of XBrn3d could cause a delay in the differentiation of precursors that give rise to sensory neurons, such that when differentiation does occur, the progenitor pool will have been expanded, resulting in generation of ectopic sensory neurons. Alternatively, since other Brn3 factors have been shown to be necessary for the survival of sensory populations, the ectopic neurons could be a result of increased survival mediated by XBrn3d. A third explanation for the presence of ectopic neurons is that XBrn3d somehow interferes with the normal migration of neural crest and differentiating sensory neurons. In the Brn3a loss-of-function mouse, the nucleus ambiguous compact formation neurons fail to migrate to the correct position in the hindbrain. The ectopic neurons seen throughout the body of XBrn3d over-expressing embryos could represent neural crest cells that were unable to migrate to the appropriate position. Finally, it is possible that XBrn3d is able to upregulate the expression of sensory neural markers in competent cells without fully changing the identity of the cells. In summary, over-expression of XBrn3d can perturb sensory neuron development. The mechanisms underlying these effects, and whether they reflect the normal in vivo function of XBrn3d, is unclear (Hutcheson, 2001).

Recent studies on vertebrate eye development have focused on the molecular mechanisms of specification of different retinal cell types during development. Only a limited number of genes involved in this process has been identified. In Drosophila, BarH genes are necessary for the correct specification of R1/R6 eye photoreceptors. Vertebrate Bar homologs have been identified and are expressed in vertebrate retinal ganglion cells during differentiation; however, their retinal function has not yet been addressed. The roles have been examined of the Xenopus Bar homolog Xbh1 in retinal ganglion cell development and its interaction with the proneural genes Xath5 and Xath3, whose ability to promote ganglion cell fate has been demonstrated. XHB1 plays a crucial role in retinal cell determination, acting as a switch towards ganglion cell fate. Detailed expression analysis, animal cap assays and in vivo lipofection assays, indicate that Xbh1 acts as a late transcriptional repressor downstream of the atonal genes Xath3 and Xath5. However, the action of Xbh1 on ganglion cell development is different and more specific than that of the Xath genes, and accounts for only a part of their activities during retinogenesis (Poggi, 2004).

The fact that Xath5 expression precedes and later partially overlaps Xbh1 expression in the CMZ, suggests a possible regulatory interaction. The animal cap assay was used to investigate whether Xbh1 can be transcriptionally regulated by Xath5. One-cell-stage embryos were injected into the animal pole with 1 ng of Xath5 RNA. Animal caps were cut at blastula stage, harvested at stage 28, and processed for RT-PCR assays to detect possible activation of Xbh1, and of the ganglion cell markers Xbrn3.0 and Xbrn3d, the earliest markers of RGCs, known as Xath5 downstream genes. Xath5 is able to activate Xbh1, Xbrn3d and Xbrn3.0 transcription in injected animal caps, whereas none of these genes was transcribed in control caps. It was also found that Xath3 is able to activate Xbh1, as well as Xbrn3.0 and Xbrn3d. Interestingly, injection of 500 pg of XneuroD mRNA, although able to trigger Xbrn3d in animal caps, is not able to activate Xbh1 expression. This suggests that Xbh1 transcription may be specifically controlled by atonal-like factors, but not by any bHLH factor (Poggi, 2004).

To test whether Xbh1 could activate Xbrn3.0 and Xbrn3d, one ng of RNA encoding Xbh1 was injected into 1-cell-stage embryos and assayed for the expression of Xbrn3 genes in stage 28 animal caps. Xbh1 was found to trigger both Xbrn3.0 and Xbrn3d transcription in animal caps. Whether Xbh1 was able to activate Xath5 and/or Xath3 was also tested in animal caps. Xbh1 does not activate Xath5, but does activate Xath3 transcription (Poggi, 2004).

Chick Brn3 genes and retinal development

Targeted gene disruption studies in the mouse have demonstrated crucial roles for the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival. During mouse retinogenesis, the Brn3b gene is expressed in a large set of postmitotic ganglion cell precursors and is required for their early and terminal differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed later in ganglion cells, appear to be dispensable for ganglion cell development. To understand the mechanism that causes the functional differences of Brn3 genes in retinal development, a gain-of-function approach was taken in the chick embryo. Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities. In Drosophila, the Brn3 homologous gene I-POU also encodes two alternatively spliced products, I-POU and tI-POU, which display similar DNA-binding properties. In the present work, Brn3b(s) functioned only as a transcriptional activator, no inhibitory effect of Brn3b(s) on the transactivation activity of Brn3a was observed. However, Brn3b(s), in some cases, is able to repress gene expression depending on the specific promoters used. The POU domain is minimally required for DNA-binding and transactivating activities. Consequently, all these Brn3 proteins have a similar ability to promote development of ganglion cells when ectopically expressed in retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b exhibits a spatial and temporal expression pattern characteristic of ganglion cell genesis and its misexpression can also increase ganglion cell production. Based on these data, it is proposed that all Brn3 factors are capable of promoting retinal ganglion cell development, and that this potential may be limited by the order of expression in vivo (Liu, 2000).

The C. elegans POU protein UNC-86, a homolog of Drosophila Acj6, specifies the HSN motor neurons, which are required for egg-laying, and six mechanosensory neurons. To investigate how UNC-86 controls neuronal specification, two unc-86 mutants have been characterized that do not respond to touch but show wild-type egg-laying behavior. Residues P145 and L195, which are altered by these mutations, are located in the POU-specific domain and abolish the physical interaction of UNC-86 with the LIM homeodomain protein, MEC-3 (most closely related to Drosophila Lim1). This results in a failure to maintain mec-3 expression and in loss of expression of the mechanosensory neuron-specific gene, mec-2. unc-86-dependent expression of genes in other neurons is not impaired. It is concluded that distinct residues in the POU domain of UNC-86 are involved in modulating UNC-86 activity during its specification of different neurons. A structural model of the UNC-86 POU domain, including base pairs and amino acid residues required for MEC-3 interaction, reveals that P145 and L195 are part of a hydrophobic pocket that is similar to the OCA-B-binding domain of the mammalian POU protein, Oct-1 (Rohrig, 2000).

During retinogenesis, the Xenopus basic helix-loop-helix transcription factor Xath5 has been shown to promote a ganglion cell fate. In the developing mouse and chicken retinas, gene targeting and overexpression studies have demonstrated critical roles for the Brn3 POU domain transcription factor genes in the promotion of ganglion cell differentiation. However, the genetic relationship between Ath5 (an atonal homolog) and Brn3 genes is unknown. To understand the genetic regulatory network(s) that controls retinal ganglion cell development, the relationship between Ath5 and Brn3 genes was analyzed by using a gain-of-function approach in the chicken embryo. It was found that during retinogenesis, the chicken Ath5 gene (Cath5) is expressed in retinal progenitors and in differentiating ganglion cells but is absent in terminally differentiated ganglion cells. Forced expression of both Cath5 and the mouse Ath5 gene (Math5) in retinal progenitors activates the expression of cBrn3c following central-to-peripheral and temporal-to-nasal gradients. As a result, similar to the Xath5 protein, both Cath5 and Math5 proteins have the ability to promote the development of ganglion cells. Moreover, forced expression of all three Brn3 genes also can stimulate the expression of cBrn3c. Ath5 and Brn3 proteins are capable of transactivating a Brn3b promoter. Thus, these data suggest that the expression of cBrn3c in the chicken and Brn3b in the mouse is initially activated by Ath5 factors in newly generated ganglion cells and later maintained by a feedback loop of Brn3 factors in the differentiated ganglion cells (Liu, 2001).

The data suggest that Ath5 and Brn3 factors constitute a transcriptional cascade regulating the specification, differentiation, and survival of retinal ganglion cells. During chicken retinogenesis, Cath5 may function in competent progenitors to promote commitment of ganglion cell fates and activate cBrn3c expression. The activation of cBrn3c expression in postmitotic ganglion cell precursors then promotes ganglion cell differentiation and survival. In differentiated ganglion cells, cBrn3c may activate the expression of cBrn3a and cBrn3b, and its expression may be subject to positive autoregulation and feedback control by cBrn3a and cBrn3b. During mouse retinogenesis, an analogous transcriptional cascade controls ganglion cell development. Math5 is responsible for the initiation of expression of Brn3b, which in turn activates the expression of Brn3a and Brn3c. The expression of Brn3b in differentiated ganglion cells is then maintained by a combination of autoactivation and feedback regulation by Brn3a and Brn3c. Although it remains to be determined what regulates the expression of Cath5 and Math5, multiple midline signals including Nodal signaling have been implicated in the control of ath5 expression in the developing zebrafish retina (Liu, 2001).

Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that is essential for retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. The existence of a link between Brn3b and the downstream events leading to RGC differentiation was investigated. Attempts were made to determine both the number and types of genes that depend on Brn3b for their expression. RNA probes from wild-type and Brn3b-/- E14.5, E16.5 and E18.5 mouse retinas were hybridized to a microarray containing 18,816 retina-expressed cDNAs. At E14.5, 87 genes were identified whose expression was significantly altered in the absence of Brn3b and the results were verified by real-time PCR and in situ hybridization. These genes fell into discrete sets that encoded transcription factors, proteins associated with neuron integrity and function, and secreted signaling molecules. Brn3b was found to influence gene expression in non RGCs of the retina by controlling the expression of secreted signaling molecules such as sonic hedgehog and myostatin/Gdf8. At later developmental stages, additional alterations in gene expression were secondary consequences of aberrant RGC differentiation caused by the absence of Brn3b. These results demonstrate that a small but crucial fraction of the RGC transcriptome is dependent on Brn3b. The Brn3b-dependent gene sets therefore provide a unique molecular signature for the developing retina (Mu, 2004).

Transcriptional regulatory networks that control the morphologic and functional diversity of mammalian neurons are still largely undefined. This study dissects the roles of the highly homologous POU-domain transcription factors Brn3a and Brn3b in retinal ganglion cell (RGC) development and function using conditional Brn3a and Brn3b alleles that permit the visualization of individual wild-type or mutant cells. Brn3a- and Brn3b-expressing RGCs exhibit overlapping but distinct dendritic stratifications and central projections. Deletion of Brn3a alters dendritic stratification and the ratio of monostratified:bistratified RGCs, with little or no change in central projections. In contrast, deletion of Brn3b leads to RGC transdifferentiation and loss, axon defects in the eye and brain, and defects in central projections that differentially compromise a variety of visually driven behaviors. These findings reveal distinct roles for Brn3a and Brn3b in programming RGC diversity, and they illustrate the broad utility of germline methods for genetically manipulating and visualizing individual identified mammalian neurons (Badea, 2009).

Mammalian POU domain class IV homologs

Ipou/abnormal chemosensory jump 6 - Evolutionary homologs part 2/2

Ipou/abnormal chemosensory jump 6: Biological Overview | Regulation | Developmental Biology | Effects of Mutation | References

Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.