sloppy paired 1


EVOLUTIONARY HOMOLOGS

In the Drosophila segmentation hierarchy, periodic expression of pair-rule genes translates gradients of regional information from maternal and gap genes into the segmental expression of segment polarity genes. In Tribolium, homologs of almost all the eight canonical Drosophila pair-rule genes are expressed in pair-rule domains, but only five have pair-rule functions. even-skipped, runt and odd-skipped act as primary pair-rule genes, while the functions of paired (prd) and sloppy-paired (slp) are secondary. Since secondary pair-rule genes directly regulate segment polarity genes in Drosophila, Tc-prd and Tc-slp were analyzed to determine the extent to which this paradigm is conserved in Tribolium. It was found that the role of prd is conserved between Drosophila and Tribolium; it is required in both insects to activate engrailed in odd-numbered parasegments and wingless (wg) in even-numbered parasegments. Similarly, slp is required to activate wg in alternate parasegments and to maintain the remaining wg stripes in both insects. However, the parasegmental register for Tc-slp is opposite that of Drosophila slp1. Thus, while prd is functionally conserved, the fact that the register of slp function has evolved differently in the lineages leading to Drosophila and Tribolium reveals an unprecedented flexibility in pair-rule patterning (Choe, 2007; full text of article).

The C. elegans gene pes-1 encodes a transcription factor of the forkhead family and is expressed in specific cells of the early embryo. Despite this expression, which suggest that pes-1 has to have an important regulatory role in embryogenesis, inactivation of pes-1 causes no apparent phenotype. This lack of phenotype is a consequence of genetic redundancy. Whereas a weak, transitory effect is observed upon disruption of just T14G12.4 (renamed fkh-2: a homolog of Drosophila sloppy paired) gene function, simultaneous disruption of the activity of both fkh-2 and pes-1 results in a penetrant lethal phenotype. Sequence comparison suggests these two forkhead genes are not closely related and the functional association of fkh-2 and pes-1 was explored only because of the similarity of their expression patterns. Conservation of the fkh-2/pes-1 genetic redundancy between C. elegans and the related species C. briggsae has been demonstrated. Interestingly the redundancy in C. briggsae is not as complete as in C. elegans and this could be explained by alterations of pes-1 specific to the C. briggsae ancestry. With overlapping function retained on an evolutionary time-scale, genetic redundancy may be extensive and expression pattern data could, as here, have a crucial role in characterization of developmental processes (Molin, 2000).

While molecular phylogenetic analysis has revealed likely orthologs for many of the C. elegans forkhead genes in species outside the Nematoda, no ortholog of pes-1 has yet been identified beyond Caenorhabditis, not even in the substantially complete Drosophila genome sequence. In contrast, fkh-2 is quite a close homolog of the Drosophila segmentation gene sloppy-paired (slp) and of the chordate gene Brain factor 1 (BF-1). These observations might suggest that pes-1 is a phylum-specific gene and/or that a low level of selection on pes-1 in the evolutionary history of the common ancestor of C. briggsae and C. elegans (because of genetic redundancy) might have contributed to the divergence of the pes-1 gene. Indeed, pes-1 and fkh-2 may be related by a gene duplication event that, although predating the C. elegans/C. briggsae divergence, may be much more recent than the molecular phylogenetic analysis might suggest. In addition, the anterior expression of BF-1 in chordates and of slp in Drosophila could correlate with the expression of pes-1 and fkh-2 in the AB cell lineage in C. elegans. Curiously slp also demonstrates functional redundancy, in this case as an adjacent pair of more similar genes that therefore probably originated with a relatively recent, gene duplication event (Molin, 2000).

Neuronal differentiation in the vertebrate nervous system is temporally and spatially controlled by mechanisms that are largely unknown. This study investigates the role of XBF-1, an anterior neural plate-specific winged helix transcription factor, in controlling the pattern of neurogenesis in Xenopus ectoderm. XBF-1 is more closely related to Drosophila slp1 and slp2 genes than to Drosophila forkhead. XBF-1 is approximately 80% identical at the amino acid level to the chicken qin and approximately 70% to the rat BF-1. The vertebrate BF-1 genes are very highly homologous in the DNA binding domain and the C terminus of the protein. Upstream of the DNA binding domain, homology is high in the N terminus but is followed by a divergent region of variable length, rich in homopolmeric amino acid runs, such as histidine and proline. The similarity between the Drosophila and vertebrate genes is mainly restricted to the DNA binding domain. However, an N-terminal region shows significant sequence similarity to the Drosophila slp2 protein, suggesting that it may be important for the function of the protein. In the anterior neural plate of normal embryos, prospective neurogenesis is positioned at the anterior boundary of the XBF-1 expression domain. By misexpressing XBF-1 in the posterior neural plate it has been shown that a high dose of XBF-1 has a dual effect: it suppresses endogenous neuronal differentiation in high expressing cells and induces ectopic neuronal differentiation in adjacent cells. In contrast, a low dose of XBF-1 does not suppress but instead, expands the domain of neuronal differentiation in the lateral and ventral sides of the embryo. XBF-1 regulates the expression of XSox3, X-ngnr-1, X-Myt-1 and X-Delta-1, suggesting that it acts early in the cascade leading to neuronal differentiation. A fusion of XBF-1 to a strong repressor domain (EnR) mimics most of the XBF-1 effects, suggesting that the wild type XBF-1 is a transcriptional repressor. However, fusion of XBF-1 to a strong activation domain (E1A) specifically suppresses neuronal differentiation suggesting that XBF-1 may also work as a transcriptional activator. Based on these findings, it is proposed that XBF-1 is involved in positioning neuronal differentiation by virtue of its concentration dependent, dual activity as both a suppressor and an activator of neurogenesis. The apparent non-autonomous effects of XBF-1 may be due to diffusion of mRNA from the site of injection, or alternatively to a diffusion of an inducer of neuronal differentiation (Bourgoignon, 1998).

Sequence data support the idea the XBF-1 may be a bimodal transcription factor. The N terminus of XBF-1 contains a sequence motif conserved between the Drosophila and Xenopus genes. A very similar motif is found in transactivation domain II located in the C terminus of HNF3beta, suggesting that it may be part of an N-terminal transactivation domain. In contrast, data from the chick suggest that the C terminus of qin is important for transcriptional repression in transient transfection assays. Since the entire C terminus of the protein is highly conserved between XBF-1 and qin it is likely that the repression function is also conserved (Bourgoignon, 1998 and references).

Xenopus Brain Factor 2 (XBF-2) is a winged-helix transcription factor expressed in the nervous system. Transcription first takes place in the anterior neural plate at the early neurula stage. At stage 14, XBF-2 is also transiently expressed in two stripes lateral to the midline, which could include cardiac and kidney precursors. This pattern is distinct from the neural crest markers slug or twist. At stage 21, expression begins in cells lateral to the rostral somites as well as in the neural tissue of the tailbud. By stage 36, transcripts are detected in restricted regions of the forebrain and in the temporal retina. Caudally, expression continues in the neural tissue of the tail bud. At this stage, there is also strong expression at the caudal end of the embryo on the ventral side. XBF-2 has been identified as a potent neuralizing activity in an expression cloning screen. In ectodermal explants, XBF-2 converts cells from an epidermal to a neural fate. Such explants contain neurons with distinct axonal profiles and express both anterior and posterior central nervous system (CNS) markers. In striking contrast to X-ngnR-1a or X-NeuroD, ectopic expression of XBF-2 in Xenopus embryos results in an expansion of the neural plate to the ventral midline. The enlarged neural plate consists predominantly of undifferentiated neurons. XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin, since ectodermal explants expressing these molecules exhibit strong expression of XBF-2. While XBF-2 does not upregulate the expression of secreted neural inducers, it downregulates the transcription of BMP-4, an epidermal inducer. XBF-2 acts as a transcriptional repressor and its effects can be phenocopied with either the Engrailed or Hairy repressor domain fused to the XBF-2 DNA-binding domain. A fusion of the DNA-binding domain to the activator domain of VP16 blocks the effects of XBF-2 and prevents neural plate development in the embryo. This provides evidence that a transcriptional repressor can affect both regional neural development and neurogenesis in vertebrates (Mariani, 1998).

XBF-1 is an anterior neural plate-specific, winged helix transcription factor that affects neural development in a concentration-dependent manner. A high concentration of XBF-1 results in suppression of endogenous neuronal differentiation and an expansion of undifferentiated neuroectoderm. The mechanism by which this expansion is achieved has been investigated. The findings suggest that XBF-1 converts ectoderm to a neural fate and it does so independently of any effects on the mesoderm. In addition, a high dose of XBF-1 promotes the proliferation of neuroectodermal cells while a low dose inhibits ectodermal proliferation. Thus, the neural expansion observed after high dose XBF-1 misexpression is due both to an increase in the number of ectodermal cells devoted to a neural fate and an increase in their proliferation. The effect on cell proliferation is likely to be mediated by p27XIC1, a cyclin-dependent kinase (cdk) inhibitor. p27XIC1 is expressed in a spatially restricted pattern in the embryo, including the anterior neural plate, and when misexpressed it is sufficient to block the cell cycle in vivo. p27XIC1 is transcriptionally regulated by XBF-1 in a dose-dependent manner such that it is suppressed or ectopically induced by a high or low dose of XBF-1, respectively. However, while a low dose of XBF-1 induces ectopic p27XIC1 and ectopic neurons, misexpression of p27XIC1 does not induce ectopic neurons, suggesting that the effects of XBF-1 on cell fate and cell proliferation are distinct. p27XIC1 is suppressed by XBF-1 in the absence of protein synthesis, suggesting that at least one component of p27XIC1 regulation by XBF-1 may be direct. Thus, XBF-1 is a neural-specific transcription factor that can independently affect both the cell fate choice and the proliferative status of the cells in which it is expressed (Hardcastle, 2000).

The forkhead domain containing transcription factor BF-1 has been shown to play a major role in the correct development of the cerebral hemispheres in the mouse. BF-1 orthologs have been isolated from zebrafish and the cephalocordate amphioxus. In both species, BF-1 is expressed in the anterior neural tube. In zebrafish, zBF-1 expression is restricted to anterior portions of the otic vesicle and to the presumptive telencephalon. In amphioxus, AmphiBF-1 is transiently seen in the frontal part of the first somite and, at 3 days of development, in a small number of cells in the cerebral vesicle. The anterior expression of BF-1 in chordates and vertebrates and of slp-1/2 in Drosophila suggests that BF-1 is crucial for an evolutionarily conserved specification of anterior neuronal cell types (Toresson, 1998).

Brain factor 1 (BF-1), a new member of the forkhead family, has been isolated from rat brain. The gene exhibits an expression pattern and DNA binding specificity distinct from the HNF-3 genes. Expression is highly restricted in the developing neural tube to the rostral end, which gives rise to the telencephalon. These results suggest that BF-1 plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon (Tao, 1992).

Three inductive interactions result in the regionalization of the mouse forebrain: (1) medial (ventral) patterning signals originating from the notochord and the more anterior precordal plate induce the primordia of the basal plate; (2) local signals arising from the anterior neural ridge (ANR), including Fgf8, induce expression of BF1, which regulates the development of specific forebrain structures such as telencephalic and optic vesicles, and (3) lateral (dorsal) patterning signals (BMPs) that arise from the non-neural ectoderm flanking the neural plate induce expression of Msx1 and patterning of the alar plate. This paper deals with the first two of these inductive interactions. Molecular properties of the medial neural plate are regulated by signals originating from the prechordal plate perhaps through the action of Sonic Hedgehog. Sonic induces homeobox gene Nkx2.1 (a homolog of Drosophila vnd) in the medial part of the mouse prosencephalic neural plate as early as the 3-somite stage, and Pax6 is expressed more laterally at similar or slighty later times. HNF3beta and not Nkx2.1 is expressed in posterior parts of explants, demonstrating that this tissue responses to Sonic and is not competent to express Nkx2.1. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system (Shimamura, 1997).

Gene expression in the antero-lateral neural plate (the anterior neural ridge is the junction between the anterior neural plate and anterior non-neural ectoderm) is regulated by non-neural ectoderm and bone morphogenetic proteins. BF1 expression is first detectable as early as the 3-somite-stage in the non-neural ectoderm underlying the anterior margin of the neural plate. By the 8-somite-stage, the expression is also detectable in the anterolateral neural plate. BF-1 expression in the developing brain is restricted to the telencephalic neuroepithelium and the nasal half of the retina and optic stalk. Its expression domain is adjacent to that of BF-2, which is restricted to the rostral diencephalon and the temporal half of the retina and optic stalk. Thus, the anterior neural ridge regulates patterning of the anterior neural plate, through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1; this neural ridge expresses Fgf8. Recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives (Shimamura, 1997).

The neural plate is subdivided into distinct anterior-posterior domains that have different responses to inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. For example, Engrailed 2 is induced by beads placed more posteriorly than those that induce BF1. The induced BF1-expression domain is delineated posteriorly by a sharp boundary, which may be orthogonal to the long axis of the explants. The posterior boundary of BF1 and the anterior boundary of En2 are nearly adjacent. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate; (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization (Shimamura, 1997).

Brain factor 1 (BF-1) is a winged-helix transcriptional repressor that plays important roles in both progenitor cell differentiation and regional patterning in the mammalian telencephalon. The aim of this study was to elucidate the molecular mechanisms underlying BF-1 functions. BF-1 has been shown to interact in vivo with global transcriptional corepressors of the Groucho family and also associates with the histone deacetylase 1 protein. The ability of BF-1 to mediate transcriptional repression is promoted by Groucho and inhibited by the histone deacetylase inhibitor trichostatin A, suggesting that BF-1 recruits Groucho and histone deacetylase activities to repress transcription. These studies also provide the first demonstration that Groucho mediates a specific interaction between BF-1 and the basic helix-loop-helix protein Hes1 and that BF-1 potentiates transcriptional repression by Hes1 in a Groucho-dependent manner. These findings suggest that Groucho participates in the transcriptional functions of BF-1 by acting as both a corepressor and an adapter between BF-1 and Hes1. Taken together with the demonstration that these proteins are coexpressed in telencephalic neural progenitor cells, these results also suggest that complexes of BF-1, Groucho, and Hes factors may be involved in the regulation of progenitor cell differentiation in the telencephalon (Yao, 2001).

The winged helix transcription factor FoxG1 (Bf-1, qin) plays multiple roles in the development of the telencephalon, with different parts of the protein affecting either proliferation or differentiation. The consequences were examined of over-expression, via retroviral expression, of FoxG1 on the growth of different regions of the chicken brain. Excess expression of FoxG1 causes a thickening of the neuroepithelium, and ultimately large outgrowths of the telencephalon and mesencephalon. In contrast, the myelencephalon appears unaffected, exhibiting normal apoptosis and growth characteristics. A DNA binding defective form of FoxG1 does not exhibit these abnormalities, suggesting that these effects are due to FoxG1's function as a transcriptional repressor. To examine the means by which excess FoxG1 causes overgrowth of the brain, alterations in cell proliferation and death were examined. No increase in proliferation was noted in any portion of the neural tube, rather a significant decrease in neuroepithelial apoptosis was seen. These results demonstrate a previously unrecognized role for winged helix factors in the regulation of neural cell apoptosis (Ahlgren, 2003).

PLU-1 is a large (1544 amino acids) nuclear protein that is highly expressed in breast cancers and is proposed to function as a regulator of gene expression. A yeast two-hybrid screen using PLU-1 as bait has identified two unrelated PLU-1 interacting proteins, namely brain factor-1 (BF-1) and paired box 9 (PAX9), both of which are developmental transcription factors. BF-1 and PAX9 interact with PLU-1 via a novel conserved sequence motif (Ala-X-Ala-Ala-X-Val-Pro-X4-Val-Pro-X8-Pro, termed the VP motif), because deletion or site-directed mutagenesis of this motif in either protein abolishes PLU-1 interaction in vivo. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression. Mutation of the PLU-1 binding motifs in BF-1 and PAX9 abolishes the observed PLU-1 co-repression activity. These data support a role for PLU-1 acting as a transcriptional co-repressor of two unrelated developmental transcription factors. Because both BF-1 and PAX proteins interact with members of the groucho co-repressor family, it is plausible that PLU-1 has a role in groucho-mediated transcriptional repression (Tan, 2003).

During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. The generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, an excess of Cajal-Retzius neuron production in the cortex is observed. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, Foxg1 is demonstrated to be constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost (Hanashima, 2004).

During normal development, retinal ganglion cells (RGCs) project axons along the optic nerve to the optic chiasm on the ventral surface of the hypothalamus. In rodents, most RGC growth cones then cross the ventral midline to join the contralateral optic tract; those that do not cross join the ipsilateral optic tract. Contralaterally projecting RGCs are distributed across the retina whereas ipsilaterally projecting RGCs are concentrated in temporal retina. The transcription factor Foxg1 (also known as BF1) is expressed at several key locations along this pathway. Analysis of Foxg1 expression using lacZ reporter transgenes shows that Foxg1 is normally expressed in most, if not all, nasal RGCs but not in most temporal RGCs, neither at the time they project nor earlier in their lineage. Foxg1 is also expressed at the optic chiasm. Mice that lack Foxg1 die at birth and, although the shape of their eyes is abnormal, their retinas still project axons to the brain via the optic chiasm. Using anterograde and retrograde tract tracing, it has been shown that there is an eightfold increase in the ipsilateral projection in Foxg1-/- embryos. The distributions of cells expressing the transcription factors Foxg1 and Nkx2.2, and cell-surface molecules Ephb2, ephrin B2 and SSEA-1 (Fut4) have been correlated to the normally developing retinothalamic projection, and they are not much altered in the developing Foxg1-/- retina and optic chiasm. Since much of the increased ipsilateral projection in Foxg1-/- embryos arises from temporal RGCs that are unlikely to have an autonomous requirement for Foxg1, it is proposed that the phenotype reflects at least in part a requirement for Foxg1 at the optic chiasm (Pratt, 2004).

Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells

It has been shown that defined sets of transcription factors are sufficient to convert mouse and human fibroblasts directly into cells resembling functional neurons, referred to as 'induced neuronal' (iN) cells. For some applications however, it would be desirable to convert fibroblasts into proliferative neural precursor cells (NPCs) instead of neurons. It was hypothesized that NPC-like cells may be induced using the same principal approach used for generating iN cells. Toward this goal, mouse embryonic fibroblasts derived from Sox2-EGFP mice were transfected with a set of 11 transcription factors highly expressed in NPCs. Twenty-four days after transgene induction, Sox2-EGFP(+) colonies emerged that expressed NPC-specific genes and differentiated into neuronal and astrocytic cells. Using stepwise elimination, it was found that Sox2 and FoxG1 are capable of generating clonal self-renewing, bipotent induced NPCs that gave rise to astrocytes and functional neurons. When the Pou and Homeobox domain-containing transcription factor Brn2 to was added Sox2 and FoxG1, it was possible to induce tripotent NPCs that could be differentiated not only into neurons and astrocytes but also into oligodendrocytes. The transcription factors FoxG1 and Brn2 alone also were capable of inducing NPC-like cells; however, these cells generated less mature neurons, although they did produce astrocytes and even oligodendrocytes capable of integration into dysmyelinated Shiverer brain. These data demonstrate that direct lineage reprogramming using target cell-type-specific transcription factors can be used to induce NPC-like cells that potentially could be used for autologous cell transplantation-based therapies in the brain or spinal cord (Lujan, 2012).

Integration of telencephalic Wnt and Hedgehog signaling center activities by Foxg1

The forebrain is patterned along the dorsoventral (DV) axis by Sonic Hedgehog (Shh). However, previous studies have suggested the presence of an Shh-independent mechanism. This study identifies Wnt/β-catenin (activated from the telencephalic roof) as an Shh-independent pathway that is essential for telencephalic pallial (dorsal) specification during neurulation. The transcription factor Foxg1 coordinates the activity of two signaling centers: Foxg1 is a key downstream effector of the Shh pathway during induction of subpallial (ventral) identity, and it inhibits Wnt/β-catenin signaling through direct transcriptional repression of Wnt ligands. This inhibition restricts the dorsal Wnt signaling center to the roof plate and consequently limits pallial identities. Concomitantly to these roles, Foxg1 controls the formation of the compartment boundary between telencephalon and basal diencephalon. Altogether, these findings identify a key direct target of Foxg1, and uncover a simple molecular mechanism by which Foxg1 integrates two opposing signaling centers (Danesin, 2009).

The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice

Foxg1 is required for development of the ventral telencephalon in the embryonic mammalian forebrain. Although one existing hypothesis suggests that failed ventral telencephalic development in the absence of Foxg1 is due to reduced production of the morphogens sonic hedgehog (Shh) and fibroblast growth factor 8 (Fgf8), the possibility that telencephalic cells lacking Foxg1 are intrinsically incompetent to generate the ventral telencephalon has remained untested. The ability of Foxg1-/- telencephalic cells to respond to Shh and Fgf8 was tested by examining the expression of genes whose activation requires Shh or Fgf8 in vivo and by testing their responses to Shh and Fgf8 in culture. It was found that many elements of the Shh and Fgf8 signalling pathways continue to function in the absence of Foxg1 but, nevertheless, it was not possible to elicit normal responses of key ventral telencephalic marker genes in Foxg1-/- telencephalic tissue following a range of in vivo and in vitro manipulations. The development of Foxg1-/- cells was examined in Foxg1-/- Foxg1+/+ chimeric embryos that contained ventral telencephalon created by normally patterned wild-type cells. It was found that Foxg1-/- cells contributed to the chimeric ventral telencephalon, but that they retained abnormal specification, expressing dorsal rather than ventral telencephalic markers. These findings indicate that, in addition to regulating the production of ventralising signals, Foxg1 acts cell-autonomously in the telencephalon to ensure that cells develop the competence to adopt ventral identities (Manuel, 2010).

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. This study shows that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. TLE2 is co-expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C-terminal YWPMSPF motif. Although direct binding seems to be mediated by the N-terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon (Roth, 2010).


sloppy paired 1: 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.