- Differences in left-right axis pathways in mouse
and chick: functions of FGF8 and SHH. Meyers EN,
Martin GR Science 1999 Jul 16;285(5426):403-6 Abstract
- chicken: Left = shh, Right = FGF8
- Mouse: Left = FGF8, Right= shh inhibition of FGF8
- The SIL gene is required for mouse embryonic axial
development and left-right specification. Izraeli S,
Lowe LA, Bertness VL, Good DJ, Dorward DW, Kirsch IR,
Kuehn MR Nature 1999 Jun 17;399(6737):691-4 Abstract
- Here we show that mouse embryos lacking the
early-response gene SIL have axial midline defects, a
block in midline Sonic hedgehog (Shh) signalling and
randomized cardiac looping. Comparison with Shh mutant
embryos, which have axial defects but normal cardiac
looping, indicates that the consequences of abnormal
midline development for left-right patterning depend
on the time of onset, duration and severity of
disruption of the normal asymmetric patterns of
expression of nodal, lefty-2 and Pitx2.
- SIL= early-response gene
- Regulation of left-right asymmetries in the
zebrafish by Shh and BMP4. Schilling TF, Concordet
JP, Ingham PW Dev Biol 1999 Jun 15;210(2):277-87
- show that Shh also specifies asymmetries in
visceral precursors in the zebrafish and that cardiac
and visceral sidedness are independent.
- The transcription factors fli-1 and Nkx-2.5 are
expressed asymmetrically in the precardiac mesoderm
and subsequently in the heart; an Eph receptor, rtk2,
and an adhesion protein, DM-GRASP, mark early
asymmetries in visceral endoderm.
- Misexpression of shh mRNA, or a dominant negative
form of protein kinase A, on the right side reverses
the expression of these asymmetries in precursors of
both the heart and the viscera.
- Reversals in the heart and gut are uncoordinated,
suggesting that each organ interprets the signal
independently. Misexpression of Bone Morphogenetic
Protein (BMP4) on the right side reverses the heart,
but visceral organs are unaffected, consistent with a
function for BMPs locally in the heart field.
Zebrafish mutants with midline defects show
independent reversals of cardiac and visceral
laterality. Thus, hh signals influence the development
of multiple organ asymmetries in zebrafish and
different organs appear to respond to a central
cascade of midline signaling independently, which in
the heart involves BMP4.