BrainGenes: A search for Drosophila neuronal precursor genes

Genes with dynamic expression profiles in neural lineages

• Transcription factors and chromatin proteins
  • CG3658 (cDNA 3771) corresponds to the chromatin-binding protein encoding gene, CDC45L. Expression is detected in NBs and GMCs, during both early and late lineage development. Note, CDC45L is not expressed in neurons.
  • CG4299 (cDNA 7954), corresponds to the gene Set. SET (Suvar3-9, Enhancer-of-zeste, Trithorax) domains mediate highly conserved interactions with a specific family of proteins that display similarity with dual-specificity phosphatases. CG4299 mRNA is maternally expressed, and transcripts are detected throughout the embryo during gastrulation. By stage 10, increased levels of expression are seen in GMCs. Set mRNA is detected in precursor cells both in the CNS and PNS. By stage 13, there is a marked reduction in expression throughout the nervous system such that by stage 14 there is no detectable embryonic expression.
  • CG4978 (cDNA 7572) corresponds to the previously characterized mini chromosome maintenance 7 (mcm7) gene. Previous work has shown that mcm7 is both maternally expressed and expressed in the developing CNS. In situ hybridizations reveal that its CNS expression is restricted to most, if not all, NBs.
  • CG5838 (cDNA 4695) corresponds to the previously characterized DNA replication-related element factor (Dref). Dref has been shown to be required for normal DNA replication in both the mitotic cell cycle and endo cycle. Our in situ hybridization studies show that Dref transcripts are detected in neural precursor cells of the CNS (including NBs and GMCs) and in SOPs the PNS. No transcripts are detected in post-mitotic neurons.
  • CG6634 (cDNA 4445) encodes a T-box transcription factor previously identified as H15. Within the developing nervous system, CG6634 transcripts are first detected in late stage 12 embryos within a single neuron per hemisegment located in the ventral column (flanking the midline). Based on the late onset of expression and the apical position of the cell body of each neuron within the ventral cord, these neurons are likely to be born during late sublineage development.
  • CG6930 (cDNA 4909) encodes a putative zinc finger transcription factor. Expression is restricted to CNS neurons and a subset of PNS neurons.
  • CG7372 (cDNA 2048) encodes a putative zinc finger transcription factor. Expression is detected in most, if not all, CNS GMCs during NB lineage development.
  • CG9045 (cDNA 6315) corresponds to the previously characterized Myb oncogene-like (Myb). In addition to the previously described maternal expression, our studies show that Myb is zygotically expressed in most if not all GMCs, however expression is not detected in post-mitotic.
  • CG9135 (cDNA 0952) is a putative guanine nucleotide exchange factor, with a potential function in protein transport/and or chromatin structure. CG9135 is maternally expressed. By embryonic stage 9, zygotic expression is detected in CNS GMCs throughout the ventral cord and cephalic lobes. CG9135 is also expressed in PNS secondary precursor cells. From stage 12-14 the mRNA is pan-neurally expressed both in precursor cells and nascent neurons. Starting at stage 14, there is marked downregulation of steady state mRNA levels, and by stage 15, only a subset of CNS and PNS neural precursors express detectable levels of the mRNA.
  • CG18783 (cDNA 4411) encodes the zinc finger transcription factor Kruppel homolog 1 Kr-h1 is expressed in CNS and PNS neurons.
  • CG9403 (cDNA 4554) encodes a zinc finger domain containing protein called Jing. During embryonic development, expression is detected in a subset of putative glial cells within the ventral cord midline and also in clusters of putative glial cells in the brain.
  • CG9745 (cDNA 4929) corresponds to the previously characterized D1 chromosomal protein, a member of the HMGI/Y family of DNA-binding proteins. In situ hybridization studies show that D1 is maternally expressed and the signal is found throughout the embryo and persists during gastrulation. However, by stage 10 increased levels of expression are seen in GMCs. D1 mRNA is detected in precursor cells both in the CNS and PNS. Starting at stage 13 there is a marked reduction in expression throughout the nervous system such that by Stage 14 there is no detectable expression.
  • CG10016 (cDNA 4820) encodes a zinc finger protein, termed Drum, related to Odd-skipped. Prior to gastrulation CG10016 expression is first detected in seven segmental bands with the most posterior stripe being the broadest. During gastrulation the number of segmental stripes increases to 15. At stage 8, expression is detected in a subset of NBs within the ventral cord. CG10016 is expressed in both the anterior and posterior gut invaginations.
  • CG11922 (cDNA 6009) corresponds to the fork head domain 96Cb gene. CG11922 expression is first activated in a single NB in the medial/ventral NB column. Expression is also detected in adjacent GMCs. Expression is then activated in additional NBs and GMCs that occupy the intermediate and lateral columns of each hemisegment. During stages 13-15 expression is restricted to a subset of neurons in each hemisegment.

• Genes that encode putative RNA-binding proteins
  • CG4396 (cDNA 4615) encodes the nuclear RNA-binding protein Fne. At stage 12/4, expression is first detected in CNS neurons. No expression is observed outside of the CNS.
  • CG32423 (cDNA 5319) encodes a protein that harbors two RNA-binding motifs. CG32423 is transiently expressed in a sheet of cells just posterior to the anterior gut invagination on the ventral side of the embryo during germ-band extension. At stage 11, expression is evident in a subset of ventral midline cells and two putative GMCs per hemisegment. At early stage 13, expression is found in putative ventral cord midline neurons.
  • CG11886 (cDNA 2255) is a homolog of vertebrate histone stem-loop binding protein, an RNA-binding protein that participates in histone pre-mRNA 3' end processing. CG11886 is maternally expressed and transcripts are detected throughout the cellular blastoderm. With the exception of ventral cord and cephalic lobe neural precursors, steady state message levels of CG11886 drop during germ-band contraction. By stage 13, only cephalic lobe NBs contain significant levels of gene expression.
  • CG12749 (cDNA 6007) encodes the Heterogeneous nuclear ribonucleoprotein at 87F (Hrb87F). Expression is detected in most, if not all, CNS and PNS neurons.

• Genes that encode cytosolic proteins
  • CG1624 (cDNA 5513) encodes a protein with an N-terminal C3HC4 RING finger motif termed Dappled. During late stage 11, mRNA is detected in NBs and GMCs of the ventral cord and brain. Expression is observed throughout NB lineage development.
  • CG3427 (cDNA 8276) encodes a putative guanine nucleotide exchange factor termed Epac that exhibits both a guanine nucleotide exchange factor domain and a cAMP-binding domain. Expression is detected in a subset of ventral cord midline cells. Based on the position of the cells and morphology of their cell bodies, these cells are most likely midline glia.
  • CG4746 (cDNA 4517) encodes a protein Mab-2, homologous to C. elegans mab-21. Expression is detected in a subset of ventral cord neurons and in putative midline neurons.
  • CG6831 (cDNA 0631) encodes the Drosophila Talin homolog, termed Rhea. Expression is restricted to subset of neurons in all CNS ganglia. Talin mRNA expression is first detected in a subset of medial ventral cord neurons. During germ-band contraction expression is also detected in neurons that occupy intermediate and lateral positions in the ventral cord and in the midline. In a stage 15 embryo, expression is detected in neurons that flank the midline and clusters of lateral neurons in the ventral cord and in a subset of neurons in the cephalic lobes. No expression is observed outside the CNS.
  • CG7324 (cDNA 3753) codes for a protein with a TBC (Tre-2, BUB2p, and Cdc16p) domain, a widespread motif present in transport ATPases, giving rise to the notion that it performs a GTP-activator activity on Rab-like GTPases. CG7324 bears partial homology (significance: 9e-21) to the Drosophila Pollux protein. CG7324 expression is first detected in the cellular blastoderm in 8 segmental stripes that are excluded from the presumptive mesoderm. By germ-band extension there are 13 stripes in the ventral neurogenic region, and shortly after, at stage 9, expression is restricted to a subset of NBs that presumably originate for these segmentally arrayed neuroectodermal expression domains. By stage 11 no expression is detected in NBs, GMCs, or neurons. In stage 14 and older embryos low by detectable levels of expression are detected in ventral cord midline cells.
  • CG9379 (cDNA 3100) encodes a protein that shares homology with the C-terminal domain of Tensin (surrounding Tensin's SH2 domain). Expression is detected in subsets of segmentally arrayed NBs and their GMCs.
  • CG9999 (cDNA 6008) corresponds to the Drosophila gene Segregation distorter (Sd). Sd is a naturally occurring meiotic drive system in which the mutant Sd chromosome is transmitted from heterozygous males in vast excess owing to the induced dysfunction of Sd+-bearing spermatids. The wild-type allele of Sd encodes a RanGAP nuclear transport protein. Sd is maternally expressed and during gastrulation mRNA steady state levels decrease. By germ-band extension, expression is detected in CNS NBs and by stage 14, expression is no longer detected.
  • CG31048 (cDNA 5089) encodes a predicted protein of 2015 amino acids that is a homolog of DOCK180, a CRK-binding protein implicated in transduction of signals downstream of receptor tyrosine kinases. CG31048 is maternally expressed; during gastrulation transcripts are detected throughout the embryo. At later stages, transcripts are also found throughout the embryo, however, higher levels of transcript are detected in GMCs and nascent neurons of the CNS.

• Genes that encode putative enzymes or chaperone proteins

  • CG1444 (cDNA 3615) encodes a steroid dehydrogenase. Expression is transiently detected in a subset of GMCs both in the ventral cord and cephalic neurogenic region.
  • CG4446 (cDNA 4629) encodes a pyridoxal kinase. CG4446 is expressed in most if not all NBs throughout lineage development. No expression is detected in GMCs or neurons.
  • CG5235 (cDNA 7970) is related to dopamine beta-hydroxylase, the enzyme catalyzing the conversion of dopamine to norepinephrine. CG5235 is maternally expressed, however during gastrulation mRNA steady state levels are significantly diminished. Expression is next detected in NBs and GMCs, however no expression is detected in neurons. During stage 13 transient expression can also be detected in secondary SOPs of the PNS.
  • CG5358 (cDNA 6002) encodes a homolog of mammalian Coactivator-associated arginine methyltransferase. Expression is limited to NBs and GMCs during late NB sublineage development.
  • CG10160 (cDNA 5602) corresponds to the characterized Ecdysone-inducible gene L3 (IMP-L3), a 20-hydroxyecdysone-responsive gene that encodes lactate dehydrogenase. Al late stage 7 IMP-L3 expression is observed in all early delaminating CNS NBs. During stage 11,IMP-L3 expression is detected in two adjacent NBs within each ventral cord hemisegment. Aligned with these NBs (in the AP axis) is a single midline cell expressing IMP-L3 mRNA
  • CG11958 (cDNA 3999) corresponds to Calnexin99A. Calnexin99A expression is restricted to longitudinal and midline CNS glia, based on cell morphology and the dorsal position of the cells within the developing ganglia.

• Genes that encode transmembrane and extracellular proteins

  • CG2446 (cDNA 5311) encodes a 550 amino acid protein that has an N-terminal domain similar to the Arabidopsis protein AAG51077. Within this N-terminal domain, both the Drosophila and Arabidopsis proteins possess a predicted TM region. CG2446 is maternally expressed and during later stages of development transcripts are also found throughout the embryo. However, higher levels of expression are detected in GMCs and nascent neurons of the CNS.
  • FlyBase">CG2893 (cDNA 0941) encodes a predicted sodium/calcium exchange protein. CG2893 expression is detected in a subset of cells in the CNS and PNS. These cells appear to be glial cells based on their cell body morphologies and positions.
  • CG3624 (cDNA 4312) encodes a predicted Ig domain protein of 168 amino acids most closely resembling, in length and sequence, Glial growth factor (E-value = 0.01). However, the overall sequence homology is low (only 26% identity at the amino acid level). During CNS development CG3624 mRNA is expressed in most if not all GMCs. Later in embryonic development transcripts are detected in lateral skeletal muscle, and by stage 14 in a subset of cells lining the posterior gut.
  • CG5670 (cDNA 3543) corresponds to the previously characterized Sodium pump a subunit. Expression is detected in a subset of medial and lateral ventral cord neurons.
  • CG6151 (cDNA 2125) encodes a protein of 192 amino acids. Two related predicted proteins are found in NCBI database, one from C. elegans (NCBI accession T21142: 44% aa identity) and one from humans (NCBI accession CAB66156: 35% aa identity). Hydrophobicity analysis of the CG6151 predicted protein reveals three potential TM domains. Embryo in situ hybridizations reveal expression is first detected in most, if not all, nascent neurons during germ-band retraction, both in the CNS and PNS. By stage 15 transcripts are detected in most if not all neurons.
  • CG6890 (cDNA 2273) encodes Tollo, a Toll-like receptor. Tollo mRNA is segmentally expressed in 8 bands. Each of the expression bands is broader in the neurogenic region than in the presumptive mesoderm. By germ-band extension, expression is seen in 15 stripes in the neuroectoderm, with additional expression in the cephalic region.
  • CG10577 (cDNA 5082) encodes a putative sec7 domain protein termed Loner, implicated in vesicular trafficking. In cellular blastoderm embryos, CG10577 mRNA is detected in the lateral neurogenic region, but is excluded from the presumptive mesoderm. During germ-band extension CG10577 is activated in the neuroectoderm of both the cephalic neurogenic region and in the ventral neuroectoderm.
  • CG13920 (cDNA 5701) encodes a putative transmembrane protein with four potential TM domains. CG13920 expression is restricted to CNS NBs and GMCs during late NB lineage development.
  • CG31640 (cDNA 3635) encodes a receptor protein tyrosine kinase. CG31640 mRNA expression is detected in a subset of CNS neurons. Expression is also detected in PNS neurons, developing gut and in cells that line the epidermal segment invaginations.
  • CG16876 for a receptor-like protein with four EGF domains and a single transmembrane domain, CG16876 has been named quattro, referring to the presence of four EGF domains in the encoded protein. quattro expression is restricted to macrophages that surround the developing brain and ventral cord ganglia.
  • CG18111 (cDNA 0644) encodes a member of the PBP/GOBP family of odorant- and pheromone-binding proteins. There is a segmental pattern of expression in 13 stripes in the neuroectoderm; ventral cord NBs underlying the segmental stripes also express CG18111. Expression is also evident in a subset of head NBs.

• Genes coding for novel proteins

  • CG2083 (cDNA 3782) encodes a novel protein possessing a proline rich motif and a nuclear localization signal. Expression is detected in most, if not all, CNS and PNS neurons.
  • CG2207 (cDNA 7842) corresponds to the gene l(2)k05815, and is also termed anon-fast-evolving-1A4. This novel protein of 183 aa is rich in Ala and Glu residues. CG2207 is maternally expressed and steady state mRNA levels are high throughout the embryo during germ-band elongation. However, during germ-band retraction there is a marked decline of steady-state mRNA levels such that by stage 13 significant levels of transcripts can be detected only in CNS GMCs and neurons and PNS secondary precursors and neurons. During stages 14 and 15 expression is detected in CNS neurons and in the gonads.
  • CG5746 (cDNA 4851) encodes a novel protein with a single predicted TM domain. Expression is detected in neurons throughout the CNS and a subset of neurons in the antenno-maxillary complex.
  • CG6520 (cDNA 4973) encodes a novel protein of 176 amino acids. The N-terminus of the protein is rich in glutamine and proline. CG6520 is maternally expressed and high levels of expression are detected throughout the embryo during gastrulation. However, starting at stage 12 the steady state mRNA levels are reduced except for CNS neurons.
  • CG7590 (cDNA 3932), corresponds to the gene scylla. Scylla (GenBank ID: AAF59841) codes for a protein of 280 amino acids. scylla is not maternally expressed but it is ubiquitously expressed during gastrulation. Expression fades during germ-band contraction such that by stage 14 mRNA is detectable in a subset of CNS and PNS neurons. In the ventral cord transcript is arrayed in a segmental pattern in subsets of neurons; at stage 14, CG7590 transcript is apparent in six neurons per hemisegment and is also found in a subset of neurons in the cephalic lobe.
  • CG9894 (cDNA 4071) encodes a novel protein with a predicted nuclear localization signal. Expression is detected in most, if not all, CNS neurons but only in a subset of PNS neurons. By stage 14, expression is no longer detected in the lateral PNS, however mRNA is detected in the antenno-maxillary complex where expression persists through stage 15.
  • CG13333 (cDNA 3689) codes for a novel protein of 389 amino acids. The predicted protein has homopolymeric runs of aspartic acid and threonine and a region rich in glutamic acid. The protein has an N-terminal hydrophilic region. CG13333 is maternally expressed at a low level that fades during gastrulation. Starting at stage 9, expression is activated in a continuous row of ventral cord midline cells; this expression is maintained until stage 14. Starting at stage 10 and continuing through stage 13, CG13333 transcripts are detected in a sub-set of neural precursor cells in the cephalic lobe. In addition, from stage 9 through stage 12, CG13333 is expressed in cells that line the tracheal invaginations.
  • CG14042 (cDNA 5459) encodes a novel protein. It is listed in FlyBase as a gene of uncertain existence. Expression is restricted to NBs and GMCs during late NB lineage development.
  • CG17724 (cDNA 3406) encodes a novel protein. Expression is detected in most, if not all, GMCs, however, expression appears to be short-lived in nascent neurons.

• Genes not predicted in the BDGP database

  • cDNA 2043 corresponds to a polyadenylated transcript for which there is no gene defined in the BDGP. Expression is detected in NBs and GMCs in the CNS and in SOPs of the PNS.
  • cDNA 5187 is not represented by any other cDNA in the BDGP database and does not correspond to a known predicted gene. The 5187 gene is 3' of the kinase Lk6, and the transcript terminates 1284 bases 3' of the Lk6 ORF. While potential ORFs are present in the 5187 sequence, BLASTX reveals no homologies to known proteins. mRNA expression is first detected in nascent neurons during early stage 12, and by stage 13 expression is detected in both CNS and PNS neurons. High transcript levels persist through stage 15.

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