Transcriptional control of Rohon‐Beard sensory neuron development at the neural plate border

Abstract

Rohon-Beard (RB) mechanosensory neurons are among the first sensory neurons to develop, and the process by which they adopt their fate is not completely understood. RBs form at the neural plate border (NPB), the junction between neural and epidermal ectoderm, and require the transcription factor prdm1a. Here, we show that prior to RB differentiation, prdm1a overlaps extensively with the epidermal marker dlx3b but shows little overlap with the neuroectodermal markers sox3 and sox19a. Birthdating analysis reveals that the majority of RBs are born during gastrulation in zebrafish, suggesting that it is during this period that RBs become specified. Expression analysis in prdm1a and neurogenin1 mutant and dlx3b/dlx4b morpholino-injected embryos suggests that prdm1a is upstream of dlx3b, dlx4b, and neurogenin1 at the NPB. mRNA for neurogenin1 or dlx3b/dlx4b can rescue the lack of RBs in prdm1a. Based on these data we suggest a preliminary gene regulatory network for RBs development.

Differential distribution of competence for panplacodal and neural crest induction to non-neural and neural ectoderm

“…Our loss-of-function experiments show that Dlx3 and GATA2 are required for the expression of epidermal, panplacodal and dedicated placodal markers, as well as for neural crest induction and the maintenance of neural plate border markers, confirming and significantly extending previous studies (McLarren et al, 2003;Woda et al, 2003;Kaji and Artinger, 2004;Esterberg and Fritz, 2009;Rossi et al, 2009;Kwon et al, 2010). However, neither Dlx3 nor GATA2 is expressed in the neural plate or neural crest territory, indicating that they promote neural crest or neural plate border development in a non-cell-autonomous manner (see also McLarren et al, 2003;Kaji and Artinger, 2004;Rossi et al, 2009), e.g.…”

“…Indeed, Dlx3/Dlx5 and GATA2/GATA3 have been implicated in positioning the neural plate border and are required for induction of panplacodal markers (Pera et al, 1999;McLarren et al, 2003;Woda et al, 2003;Linker et al, 2009;Esterberg and Fritz, 2009;Kwon et al, 2010). However, Dlx3/Dlx5 are also required for induction of neural crest and Rohon Beard neurons, while the effects of GATA factors on neural crest development have not been studied (McLarren et al, 2003;Woda et al, 2003;Kaji and Artinger, 2004;Rossi et al, 2009). Moreover, Dlx3/Dlx5 overexpression in neural ectoderm was insufficient to upregulate epidermal and most panplacodal markers (McLarren et al, 2003;Woda et al, 2003).…”

Prdm1a directly activates foxd3 and tfap2a during zebrafish neural crest specification

“…The subsequent gene cascade for NCC specification is well characterized, with foxd3 and tfap2a required for the expression of additional early neural crest genes including snai1b and sox10. From our work, we now know that Prdm1a, possibly along with other transcriptional regulators and/or cofactors, is directly upstream of foxd3 and tfap2a and is potentially a master regulator of the initiating steps in the specification of NCCs from the NPB in addition to potentially regulating specification of the NPB itself (Rossi et al, 2009). Prdm1a might also have a role in repressing genes that are inhibitors of NCC specification and appears to regulate NCCs after their initial specification; its action as both a transcriptional activator and repressor of genes is required for migratory NCCs.…”

“…Single-embryo genotyping of prdm1a −/− following ISH was performed as described (Rossi et al, 2009). DIG-conjugated antisense probes were synthesized from full-length transcript sequences in the pCS2+ plasmid to the following genes: snai1b (primers 5Ј-GCTAGGGATCCGCCGCCA -CCATGCCACGCTCATTTC TTGTCA-3Ј and 5Ј-GAATTCTAGATG -TGTGTCCACTAGAGCGCC-3Ј); foxd3 (see above); sox10 (Olesnicky et al, 2010); crestin (Rubinstein et al, 2000); and tfap2a (from T. Williams).…”

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

“…In zebrafish the established neural plate border specifiers include msxb, msxc, msxe and prdm1a. 202,203 Knockdown of msxb, msxc and msxe together leads to the loss of slug/snail2 and sox10, expression, but leaves expression of foxd3, dlx3b and dlx4b intact; they are required for Rohon-Beard sensory neurons and placode fate but not neural crest cell directly. 202,204,205 Other genes in this part of the network have not yet been tested for their role in neural crest development.…”