Fig. 2

Transcriptional control of sympathetic neuron development. a Target genes regulated by Phox2b in sympathetic progenitors are detected in the Phox2b-knockout mouse [140]. Solid black arrows indicate complete absence of the indicated target genes in mutant embryos. In addition to the noradrenergic marker genes Th and Dbh (noradrenergic genes labeled by blue boxes), the cholinergic markers ChAT and VAChT (cholinergic genes labeled by red boxes) are not expressed in Phox2b mouse mutants [142]. Phox2b does not control initial expression of Ascl1 (white box). Expression of the transcription factor Hand2, which is required for Th and Dbh expression [223] depends on Phox2b [224]. Expression of Gata3, which increases Th transcript levels also depends on Phox2b [173]. Embryonic overexpression demonstrates that each of the transcription factors Phox2b, Phox2a, Hand2 and Gata3 is able to induce the expression of any of the other factors in progenitor cells [173, 225, 226] (blue stippled arrows). b In differentiated neurons different target genes are regulated by Phox2b as detected in conditional mutant mice deleting Phox2b after initial differentiation [152]. In differentiated sympathetic neurons Phox2b enhances its own expression but is dispensable for Phox2a and Hand2 yet remains required for Gata3 expression. Markers for the cholinergic phenotype as VAChT, Vip and Ret (cholinergic genes labeled by red boxes) appear independent of Phox2b, as well as the generic neuronal marker Tubb3 (generic neuronal genes are indicated by green boxes). On the other hand, peripherin (Prph) and Dbh depend on Phox2b. Hand2 remains required for Th and Dbh expression (noradrenergic genes labeled by blue boxes) in differentiated embryonic sympathetic neurons [149]. Notably, Hand2 elimination in adult sympathetic neurons reveals still another set of target-genes involved in synapse function [147]