C. Biben et Rp. Harvey, HOMEODOMAIN FACTOR NKX2-5 CONTROLS LEFT RIGHT ASYMMETRIC EXPRESSION OF BHLH GENE EHAND DURING MURINE HEART DEVELOPMENT/, Genes & development, 11(11), 1997, pp. 1357-1369
One of the first morphological manifestations of left/right (L/R) asym
metry in mammalian embryos is a pronounced rightward looping of the li
near heart tube. The direction of looping is thought to be controlled
by signals from an embryonic L/R axial system. We report here that mor
phological L/R asymmetry in the murine heart first became apparent at
the linear tube stage as a leftward displacement of its caudal aspect.
Beginning at the same stage, the basic helix-loop-helix (bHLH) factor
gene eHand was expressed in a strikingly left-dominant pattern in myo
cardium, reflecting an intrinsic molecular asymmetry. In hearts of emb
ryos lacking the homeobox gene Nkx2-5, which do not loop, left-sided e
Hand expression was abolished. However, expression was unaffected in S
c1(-/-) hearts that loop poorly because of hematopoietic insufficiency
, and was right-sided in hearts of inv/inv embryos that display situs
inversus. The data predict that eHand expression is enhanced in descen
dants of the left heart progenitor pool as one response to inductive s
ignaling from the L/R axial system, and that eHand controls intrinsic
morphogenetic pathways essential for looping. One aspect of the intrin
sic response to L/R information falls under Nkx2-5 homeobox control.