foxD5 plays a critical upstream role in regulating neural ectodermal fate and the onset of neural differentiation

Abstract

foxD5 is expressed in the nascent neural ectoderm concomitant with several other neural-fate specifying transcription factors. We used loss-of-function and gain-of-function approaches to analyze the functional position of foxD5 amongst these other factors. Loss of FoxD5 reduces the expression of sox2, sox11, soxD, zic1, zic3 and Xiro1-3 at the onset of gastrulation, and of geminin, sox3 and zic2, which are maternally expressed, by late gastrulation. At neural plate stages most of these genes remain reduced, but the domains of zic1 and zic3 are expanded. Increased FoxD5 induces geminin and zic2, weakly represses sox11 at early gastrula but later (st12) induces it; weakly represses sox2 and sox3 transiently and strongly represses soxD, zic1, zic3 and Xiro1-3. The foxD5 effects on zic1, zic3 and Xiro1-3 involve transcriptional repression, whereas those on geminin and zic2 involve transcriptional activation. foxD5’s effects on geminin, sox11 and zic2 occur at the onset of gastrulation, whereas the other genes require earlier foxD5 activity. geminin, sox11 and zic2, each of which is up-regulated directly by foxD5, are all required to account for foxD5 phenotypes, indicating that this triad constitutes a transcriptional network rather than linear path that coordinately up-regulates genes that promote an immature neural fate and inhibits genes that promote the onset of neural differentiation. We also show that foxD5 promotes an ectopic neural fate in the epidermis by reducing BMP signaling. Several of the genes that are repressed by foxD5 in turn reduce foxD5 expression, contributing to the medial-lateral patterning of the neural plate.

ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis

“…Expansion of Zic2 leads to the inhibition of Xngnr-1, which normally induces expression of Myt-1 and Delta-1 to promote neurogenesis (Bellefroid et al, 1996;Brewster et al, 1998;Chitnis et al, 1995). Geminin plays a primary role in maintaining neuroectoderm in an 'immature state', conferring a reduced response to differentiation signals (Neilson et al, 2012;Yan et al, 2009;Yan et al, 2010). Geminin is highly expressed in proliferating neural progenitors (Spella et al, 2007), where it interacts with Brahmarelated gene 1 to inhibit neuronal differentiation and increase proliferation (Seo et al, 2005a;Seo et al, 2005b).…”

“…Primary neurogenesis is preceded by neural induction, which requires inhibition of bone morphogenetic protein (BMP) signaling (Wills et al, 2010;Wilson and Hemmati-Brivanlou, 1995) together with active fibroblast growth factor (FGF) signaling (reviewed by Dorey and Amaya, 2010;Marchal et al, 2009;Wills et al, 2010). Neural induction leads to the expression of proproliferative and neural-fate stabilizing transcription factors such as Foxd4l1, Geminin, Sox2/3 and Zic-family genes (Branney et al, 2009;Marchal et al, 2009;Yan et al, 2009). The concerted action of these genes promotes proliferation and maintenance of immature neural precursors.…”

AP-1c-Jun/FosBmediates xFoxD5b expression in Xenopus early developmental neurogenesis

“…1B). Previous studies reported that FoxD5a played (Yan et al, 2009a). However, the function of FoxD5b, a putative pseudo-allele gene of FoxD5a, has not yet been studied.…”

“…Later, the XFLIP has been classified into sub-families, termed XFD-12, XFD-12' and XFD-12" (Solter et al, 1999). It has been shown that FoxD5a is involved in the initiation of neural induction, but not in neuronal differentiation (Neilson et al, 2012, Yan et al, 2009a, Yan et al, 2009b, Yu et al, 2002. Recently, Neilson et al, dem-onstrated that FoxD5 regulates the transition of neuroectoderm via controlling a network of genes (Neilson et al, 2012).…”

Characterization of flounder (Paralichthys olivaceus) FoxD5 and its function in regulating myogenic regulatory factor

“…The FoxD5 can keep the neural ectoderm in undifferentiated stage after neural induction (Sullivan No (Yan et al, 2009a), gem and zic2 (Yan et al, 2009b). Experiments results suggested that the maintenance of FoxD5 expression requires bFGF, Wnt and Nodal signaling (Fetka et al, 2000).…”