Skip to main content
. Author manuscript; available in PMC: 2009 Mar 9.
Published in final edited form as: Dev Dyn. 2005 Nov;234(3):613–621. doi: 10.1002/dvdy.20544

Fig. 5. Transcriptional regulatory network during development of the ANS.

Fig. 5

During ANS development, transcription factors act in a network to induce other transcription factors. BMP is an inductive cue for the SNS lineage and activates the expression of the transcription factors Phox2b (Lo et al., 1998; Schneider et al., 1999), Mash1 (Shah et al., 1996; Lo et al., 1998) and Hand2 (Howard et al., 2000). The bHLH factor Mash1, is able to cross-activate the paired homeodomain transcription factor Phox2b (Lo et al., 1998; Lo et al., 1999) which is required for maintenance of Mash1 expression (Pattyn et al., 1999) and for expression of another bHLH factor Hand2 (Goridis and Rohrer, 2002). Hand2 activates Phox2b (Howard et al., 2000), itself and Mash1 (this study). These three factors together activate the expression of the neuronal structural genes. Each factor activates different pathways that converge during autonomic neuronal development.Generic neuronal pathway: Expression of Mash1 is sufficient for the expression of generic neuronal structural genes such as TuJ1 and NF160 (Farah et al., 2000). Mash1 is required for the expression of the noradrenergic biosynthetic genes TH, DBH (Guillemot et al., 1993) and peripherin (Sommer et al., 1995) but transcription regulation of these genes must be indirect since Mash1 expression stops at mid-gestation (Guillemot and Joyner, 1993). Neuronal type selection: Phox2b regulates expression of the zinc finger factor GATA3 (Tsarovina et al., 2004) and Phox2a (Pattyn et al., 1999). Phox2a/b and Gata3 directly regulate the expression of noradrenergic biosynthetic enzymes TH and DBH in sympathetic neurons (Kim et al., 1998; Yang et al., 1998; Lim et al., 2000) and may regulate other neuronal genes in parasympathetic and enteric neurons. Peripheral pathway: Hand2 is only expressed in the ANS lineages of the nervous system suggesting a role in its specification (Srivastava et al., 1995; Dai et al., 2004). Ectopic expression of Hand2 activates the PNS program and regulates the expression of TH in the SNS. The ability of Hand2 to activate Mash1 is p300/CBP dependent.