vHnf1 regulates specification of caudal rhombomere identity in the chick hindbrain

Abstract

The homeobox-containing gene variant hepatocyte nuclear factor-1 (vHnf1) has recently been shown to be involved in zebrafish caudal hindbrain specification, notably in the activation of MafB and Krox20 expression. We have explored this regulatory network in the chick by in ovo electroporation in the neural tube. We show that misexpression of vHnf1 confers caudal identity to more anterior regions of the hindbrain. Ectopic expression of mvHnf1 leads to ectopic activation of MafB and Krox20, and downregulation of Hoxb1 in rhombomere 4. Unexpectedly, mvhnf1 strongly upregulates Fgf3 expression throughout the hindbrain, in both a cell-autonomous and a non-cell-autonomous manner. Blockade of FGF signaling correlates with a selective loss of MafB and Krox20 expression, without affecting the expression of vHnf1, Fgf3, or Hoxb1. Based on these observations, we propose that in chick, as in zebrafish, vHnf1 acts with FGF to promote caudal hindbrain identity by activating MafB and Krox20 expression. However, our data suggest differences in the vHnf1 downstream cascade in different vertebrates. Developmental Dynamics 234:567-576, 2005.

Cdx1 refines positional identity of the vertebrate hindbrain by directly repressingMafbexpression

“…RA-dependent activation of Mafb depends, at least in part, on the homeodomain protein, variant hepatic nuclear factor 1 (vHnf1/HNF1) (Aragon et al, 2005;Hernandez et al, 2004;Kim et al, 2005;Lecaudey et al, 2004;Maves and Kimmel, 2005;Wiellette and Sive, 2003). At the 0-somite stage, Hnf1b expression, which is induced by RA, extends from the future r4/r5 boundary posteriorly into the posterior hindbrain and spinal cord of mouse, chick and zebrafish embryos (Aragon et al, 2005;Kim et al, 2005;Lecaudey et al, 2004;Maves and Kimmel, 2005). In the mouse, identification of the r5-r6 specific S5 enhancer from Mafb illustrated that vHNF1 is essential, but not sufficient, for driving r5-r6 expression in 0-to 10-somite-stage embryos.…”

Fgf3 and Fgf16 expression patterns define spatial and temporal domains in the developing chick inner ear

“…Restricted Fgf3 expression patterns in the adjacent developing hindbrain confirm this statement in several vertebrate species (zebrafish: Phillips et al 2001, 2003; Kwak et al 2002; Leger and Brand 2002; Maroon et al 2002; Maves et al 2002; Walshe et al 2002; Xenopus : Lombardo et al 1998; chick: Mahmood et al 1995; Aragón et al 2005; Kil et al 2005; Aragón and Pujades 2009; Abello et al 2010; mouse: Mahmood et al 1996; Mckay et al 1996; Pirvola et al 2000; Wright and Mansour 2003; Lin et al 2005; Hatch et al 2007). FGF3 might also participate in the complex network of intrinsic diffusible signals from the otic placode itself.…”

“…The incipient acoustic-vestibular ganglion showed a low Fgf3 expression (AVG; Fig 1a, d). In addition, Fgf3 transcripts were recognized with no trouble in the hindbrain alar plate (asterisk in Fig 1a), exclusively in the area separating contiguous rhombomeres, but not in the body of any rhombomere (rh6 in Fig 1d; see Aragón et al, 2005). …”

Hindbrain signals in otic regionalization: walk on the wild side

“…Thus, by secreting FGF signals, r4 forms a signaling centre involved in caudal hindbrain patterning, in particular in val and krox20 activation. Although Fgf gene expression patterns in the hindbrain of amniotes differ from that of zebrafish (see below), FGF signaling in chick embryos has also been involved in hindbrain patterning, particularly in the regulation of MafB and Krox20 expression (Marin and Charnay, 2000;Aragon et al, 2005).…”

“…Thus, by secreting FGF signals, r4 forms a signaling centre involved in caudal hindbrain patterning, in particular in val and krox20 activation. Although Fgf gene expression patterns in the hindbrain of amniotes differ from that of zebrafish (see below), FGF signaling in chick embryos has also been involved in hindbrain patterning, particularly in the regulation of MafB and Krox20 expression (Marin and Charnay, 2000;Aragon et al, 2005).The functional data obtained in different vertebrates can be combined into a regulatory hierarchy involved in caudal hindbrain formation (Figure 4). However, it should be mentioned that several data have been obtained in only one vertebrate species.…”