Expression and regulation of eHAND during limb development

Abstract

eHAND is a bHLH transcription factor with important functions during embryogenesis. Here, we report that eHAND has a dynamic pattern of expression during limb development. In chick embryos, eHAND expression is first observed in the ventral mesoderm of the emerging limb. Its expression is then restricted to an anteroventral area of mesoderm at mid-level in the proximodistal axis. At later stages, expression is observed in the autopod encompassing the ventral tendons of the digits. In mouse embryos, only the anteroventral domain of expression is conserved, the early ventral expression not being detectable and the late pattern of expression differing clearly from that in the chick. A constant feature of all areas of expression is their ventral and anterior localization. Respecification of the anterior mesoderm as occurs secondarily to Sonic hedgehog (SHH) or retinoic acid application to the anterior border leads to downregulation of eHAND expression. Accordingly, eHAND expression is not detectable in talpid 2 mutant limbs, which are considered to be posteriorized limbs. However, eHAND expression is little modified in oligozeugodactyly, a chick mutant that lacks Shh signaling in the limb but retains certain anteroposterior polarity. Interestingly, eHAND expression is also linked to the ventral identity of the mesoderm and is repressed by the dorsal ectoderm. It is also positively regulated by bone morphogenetic protein signaling, which is also known to participate in dorsoventral patterning. We suggest that eHAND expression may be related to the anteroventral identity of the mesoderm. However, in overexpression experiments using retroviral vectors, only a low percentage of cases (5%) showed phenotypic alterations, consisting of a duplication of digit 2. Developmental Dynamics 226:690 -701, 2003.

Analysis of the Hand1 cell lineage reveals novel contributions to cardiovascular, neural crest, extra‐embryonic, and lateral mesoderm derivatives

“…Whole mount analysis of Hand1 LacZ at later stages confirms, as has been previously reported, a late domain of expression at E12.5 in both the fore- and hindlimbs (Fig. 5I,K) (Fernandez-Teran et al, 2003). This expression of Hand1 is downregulated in the limb by E14.5 (Fig.…”

“…Hand1 is expressed, beginning at E11.5, within the anterior-ventral domain of the developing mouse limb and, by E13.5, is restricted to digit 1 (Fernandez-Teran et al, 2003). Hand1 is also expressed within the lateral mesoderm medial to the forming limb buds.…”

“…Hand1 is also expressed within the lateral mesoderm medial to the forming limb buds. Compared to Hand2 , limb expression Hand1 is greatly restricted; however, expression of these two related factors does partially overlap (Fernandez-Teran et al, 2003; Firulli et al, 2005). …”

Developmental basis for hind-limb loss in dolphins and origin of the cetacean bodyplan

“…Expression of Shh at the posterior margin of the limb bud is regulated, in part, by expression of the transcription factor Hand2. In chick and mouse embryos, Hand2 is initially expressed widely throughout the mesenchyme of the limbs and flanks but then becomes restricted to the posterior edge of the fore-and hind-limb bud, where it is a necessary condition for the expression of Shh (11)(12)(13).…”

MEF2-dependent Recruitment of the HAND1 Transcription Factor Results in Synergistic Activation of Target Promoters

“…More recently, conditional ablation of hand1 in the heart provided support for these previous observations and revealed that absence of HAND1 in cardiac myocytes leads to structural cardiac defects, consistent with an essential role in cardiomyocyte differentiation (10). Targeted gain-and loss-of-function studies have also pointed to important roles for HAND proteins in placental (6), vascular (11,13), craniofacial (14), and limb (15,16) development. However, the molecular mechanisms underlying the essential role of HAND proteins in organogenesis remain largely undefined.…”