Formation Primitive streak

1 formation

1.1 vg1 , wnt signaling
1.2 hypoblast
1.3 nodal signaling
1.4 fgf signaling
1.5 bmp signaling

formation

the formation of primitive streak relies on complex network of signaling pathways work ensure process highly regulated. activation of various secreted factors (vg1, nodal, wnt8c, fgf8 , chordin) , transcription factors (brachyury , goosecoid) adjacent site of streak formation required process. in addition, structures such hypoblast play important role in regulation of streak formation. removal of hypoblast in chick results in correctly patterned ectopic streaks, suggesting hypoblast serves inhibit formation of primitive streak.

an intricate network of signaling pathways regulate formation of primitive streak.


vg1 , wnt signaling

similarly, vg1 (a tgfb family member) misexpression , grafts of posterior marginal zone in chicks can induce ectopic streaks, within marginal zone of embryo, indicating specific characteristic of region in ability induce streak formation. several lines of evidence point wnt expression determinant of ability. deletion of wnt3 in mouse embryos results in absence of streak formation, phenotype of b-catenin mutant embryos. in addition, mutating intracellular negative regulator of wnt signaling, axin, , misexpression of chick cwnt8c produces multiple streaks in mouse embryos. localization of wnt , components of pathway, lef1 , b-catenin, further supports streak-inducing role in marginal zone. furthermore, expressed gradient decreasing posterior anterior, corresponding streak-inducing ability of marginal zone. misexpression of vg1 or wnt1 alone failed induce ectopic streak in chick, misexpression resulted in ectopic streak formation, confirming streak-inducing ability of posterior marginal zone attributed wnt signaling , vg1 , wnt must cooperate induce process. misexpression of vg1 along wnt antagonists, crescent or dkk-1, prevents formation of ectopic streaks, demonstrating importance of wnt activity in formation of vg1-induced ectopic streaks , hence implication in normal primitive streak formation.

hypoblast

any given slice blastoderm able generate complete axis until time of gastrulation , primitive streak formation. ability generate streak pre-streak stage chick embryo indicates there must mechanism ensure single streak forms. hypoblast secretes antagonist of nodal prevents ectopic streak formation in chick.

nodal signaling

nodal, known mesodermal inducer of tgfb superfamily, has been implicated in streak formation. mouse embryos mutant nodal fail gastrulate , lack mesoderm, more playing role in mesoderm induction, nodal regulates induction and/or maintenance of primitive streak. in presence of hypoblast, nodal unable induce ectopic streaks in chick embryo, while removal, induces expression of nodal, chordin , brachyury, suggesting hypoblast must have inhibitory effect on nodal signaling. indeed, multifunctional antagonist of nodal, wnt , bmp signaling, cerberus (produced in hypoblast) , cerberus-short (which inhibits nodal), through effect on nodal signaling, inhibits streak formation. eventually, hypoblast gets displaced anteriorly moving endoblast, allowing streak formation @ posterior end. @ anterior end, presence of hypoblast , antagonists secretes, such cerberus, inhibit expression of nodal , hence restrict streak formation posterior end only. hypoblast in chick, ave in mouse secretes 2 antagonists of nodal signaling, cerberus-like, cerl, , lefty1. in mouse, cer-/-; lefty1-/- double mutants develop multiple streaks indicated ectopic expression of brachyury , can partially rescued removal of 1 copy of nodal gene. in mouse, ave restricts streak formation through redundant functions of cer1 , lefty1, negatively regulate nodal signaling. role of mouse’s ave in ensuring formation of single primitive streak evolutionarily conserved in hypoblast of chick.

fgf signaling

another important pathway in modulating formation of primitive streak fgf, thought work nodal regulate process. inhibition of fgf signaling through expression of dominant negative receptor, using fgf receptor inhibitor (su5402) or depletion of fgf ligands, inhibit mesoderm formation , in turn, inhibits streak formation. furthermore, ectopic streak formation induced vg1 required fgf signaling.

bmp signaling

finally, bmp signaling important regulating process of streak formation in chick embryo. site of streak formation characterized low bmp signals, while rest of epiblast displays high levels of bmp activation. in addition, misexpression of either bmp4 or bmp7 prevents streak formation, while bmp inhibitor chordin induces ectopic streak formation in chick, suggesting streak formation require bmp inhibition.