Alternative titles; symbols
HGNC Approved Gene Symbol: SP8
Cytogenetic location: 7p21.1 Genomic coordinates (GRCh38) : 7:20,782,279-20,786,886 (from NCBI)
Treichel et al. (2003) cloned mouse Sp8, which they designated Btd due to its homology with the Drosophila 'buttonhead' (btd) transcription factor. The deduced 486-amino acid protein contains an N-terminal serine-threonine domain, followed by an alanine-rich sequence, a glycine-rich sequence, a Btd domain, and SP1 (189906)-like zinc fingers.
Bell et al. (2003) determined that the human SP8 protein, which contains 466 amino acids, shares 97% identity with the mouse protein. In situ hybridization of day-8 mouse embryos detected Sp8 in the forming neural tube. At later stages, Sp8 localized predominantly in neural tissues and in the apical ectodermal ridge (AER) of fore- and hindlimb buds.
Using in situ hybridization with embryonic and postnatal mouse brains, Waclaw et al. (2006) found that Sp8 was expressed in neurogenic regions that gave rise to olfactory bulb interneurons. Sp8 remained expressed in calretinin (CALB2; 114051)-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer.
Treichel et al. (2003) determined that mouse Sp8 mediates proximodistal outgrowth of the limb during early development. They presented evidence that Sp8 is required to maintain, but not to initiate, Wnt (see 604663)/beta-catenin (116806)-dependent Fgf (see 131220)-, Shh (600725)-, and Bmp (see 112264)-mediated signaling.
Bell et al. (2003) determined that the mouse Sp8 gene contains 3 exons. Exon 3 contains the coding region and the 3-prime UTR.
Hartz (2003) mapped the SP8 gene to chromosome 7p21 based on an alignment of the SP8 sequence (GenBank AK056857) with the genomic sequence.
By genomic sequence analysis, Bell et al. (2003) mapped the SP8 gene to chromosome 7p21-p15.
Treichel et al. (2003) generated Sp8-deficient mice, which developed to term but died at birth. They exhibited brain malformations, posterior axial skeleton truncations, and shortened limbs.
The Dnah11 (603339) and Sp4 (600540) genes upstream of Sp8 are deleted in the mouse legless (lgl) transgene insertional mutant, but gene targeting has shown that neither gene is responsible for the limb truncation or craniofacial malformations observed in lgl mutants. Bell et al. (2003) found that lgl mice showed reduced Sp8 expression, particularly in the developing hindlimbs. Consistent with this finding, Sp8 knockout in mice resulted in severe truncation of forelimbs and hindlimbs, absence of tail, and defects in anterior and posterior neuropore closure leading to exencephaly and spina bifida. In Sp8-null mice, AER precursor cells were induced and initially expressed multiple appropriate marker genes, but expression of these genes was not maintained and progression to a mature AER was blocked. Bell et al. (2003) concluded that SP8 functions downstream of WNT3 (165330), FGF10 (602115), and BMPR1A (601299) in the signaling cascade that mediates AER formation.
Waclaw et al. (2006) found that Sp8 deletion in mice resulted in severe exencephaly. Conditional deletion of Sp8 in the ventral telencephalon resulted in fewer mice displaying exencephaly, and most of these mutant mice developed morphologically normal brains with noticeably smaller olfactory bulbs. Conditional Sp8 mutants exhibited an increase in cell death within the lateral ganglionic eminence and rostral migratory stream. Mutant neuroblasts/interneurons were misspecified and displayed abnormal migration patterns in the olfactory bulb. Waclaw et al. (2006) concluded that Sp8 contributes to olfactory bulb interneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.
Bell, S. M., Schreiner, C. M., Waclaw, R. R., Campbell, K., Potter, S. S., Scott, W. J. Sp8 is crucial for limb outgrowth and neuropore closure. Proc. Nat. Acad. Sci. 100: 12195-12200, 2003. [PubMed: 14526104] [Full Text: https://doi.org/10.1073/pnas.2134310100]
Hartz, P. Personal Communication. Baltimore, Md. 12/2/2003.
Treichel, D., Schock, F., Jackle, H., Gruss, P., Mansouri, A. mBtd is required to maintain signaling during murine limb development. Genes Dev. 17: 2630-2635, 2003. [PubMed: 14597661] [Full Text: https://doi.org/10.1101/gad.274103]
Waclaw, R. R., Allen, Z. J., II, Bell, S. M., Erdelyi, F., Szabo, G., Potter, S. S., Campbell, K. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron 49: 503-516, 2006. [PubMed: 16476661] [Full Text: https://doi.org/10.1016/j.neuron.2006.01.018]