A differentiation program induced by bone morphogenetic proteins 4 and 7 in endodermal epithelial cells provides the molecular basis for efficient nutrient transport by the chicken yolk sac.

Raimund Bauer,Wolfgang J Schneider,Philipp Tondl

doi:10.1002/dvdy.129

Abstract

BackgroundThe mammalian yolk sac provides nutrients for the growing fetus during critical early developmental processes such as neural tube closure, which precedes the functional maturation of the placenta. In contrast, oviparous species such as the chicken rely solely on the yolk sac for transfer of nutrients from the yolk to the developing embryo. However, the molecular mechanisms that provide the yolk sac with nutrient transfer competence remain poorly understood.ResultsWe demonstrate that the chicken endodermal epithelial cells (EEC), which are in close contact with the yolk, gain their nutrient‐transport competence by a paracrine crosstalk with the blood‐vessel forming mesodermal cell layer. Bone morphogenetic proteins (BMP) 4 and 7 produced by ectodermal and mesodermal cell layers likely initiate a differentiation program of EECs during the transition from the area vitellina to the area vasculosa. BMPs, by inducing SMAD signaling, promote the up‐regulation of endocytic receptor expression and thereby provide the EECs with the molecular machinery to produce triglyceride‐rich lipoprotein particles.ConclusionThis paracrine signaling cascade may constitute the basis for the EEC‐mediated mechanism underlying the efficient uptake, degradation, resynthesis, and transfer of yolk‐derived nutrients into the embryonic circulation, which assures proper energy supply and development of the growing fetus.

Highlights

In amniotic vertebrates, the yolk sac is the first organ that mediates the transport of nutrients from maternal sources to the growing embryo.[1,2,3] In mammals, the yolk sac is of major importance before the formation and functional maturation of the chorioallantoic placenta, a highly critical time in embryonic development during wileyonlinelibrary.com/journal/dvdyDevelopmental Dynamics. 2020;249:222–236
We reported that the chicken yolk sac endodermal epithelial cells (EECs), which mediate the efficient uptake, degradation, and resynthesis of yolk nutrients, differentiate into a metabolically highly active type of cells as they become competent for the uptake of nutrients via mesoderm-derived blood vessels during the transition from the area vitellina to the area vasculosa.[5]
EECs and mediates efficient uptake of yolk macromolecules,[5] genes encoding apolipoproteins associated with triglyceride-rich lipoproteins (APOB, APOA5, APOA4, and APOC3) as well as with HDL-like particles (APOA1) are predominantly expressed in the EECs of the area vasculosa (Figure 1B)

Summary

| INTRODUCTION

The yolk sac is the first organ that mediates the transport of nutrients from maternal sources to the growing embryo.[1,2,3] In mammals, the yolk sac is of major importance before the formation and functional maturation of the chorioallantoic placenta, a highly critical time in embryonic development during. During murine yolk sac development, BMPs are primarily expressed in mesodermal angioblasts that eventually form the vascular network mediating nutrient transport to the embryo.[14,15] BMP4-knockout mice die between E6.5 and E9.5, with embryos showing severe developmental retardation, disorganized posterior structures, and a reduction in extraembryonic mesoderm, including yolk sac blood islands.[16] Since (a), targeted disruption of the BMP4 receptor ALK2 causes embryonic lethality, abnormal visceral endoderm morphology and disruption of mesoderm formation[17] and (b), murine blastocyst-derived extraembryonic endoderm (XEN) cells acquire features of endodermal cells of the yolk sac upon stimulation with BMP4,18,19 our major goal was the elucidation of the role of BMP signaling in yolk sac endoderm specification. As the developing chicken yolk sac represents a valuable and amenable tool to study these developmental processes in detail, we set out to shed further light on the potential of BMPs in regulating chicken yolk sac function, and in particular, EEC differentiation

| RESULTS

| DISCUSSION

| EXPERIMENTAL PROCEDURES