Modelling the role of the basement membrane beneath a growing epithelial monolayer

The role of the ectoderm in the expansion of the mesoderm in the area vasculosa of the chicken embryo was studied. The basement membrane of the ectoderm was found to constitute a substratum for the expansion of both layers of mesoderm, since (a) the somatic mesoderm, particularly at its margin, adheres to the basement membrane, and (b) the somatic and splanchnic mesoderm adhere to each other throughout most of the area opaca. Following removal of the ectoderm from the outer surface of the basement membrane, movement of the underlying mesoderm along its inner surface stopped. Mean expansion of the mesoderm in these cases was zero. Following removal of both ectoderm and basement membrane, expansion of the underlying mesoderm was normal in amount. Experimental changes in the ectodermal substratum can thus stop movement of the associated mesoderm, but the role which the substratum normally plays in mesodermal expansion remains unclear.

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Lineage-specific morphogenesis in the developing pancreas: role of mesenchymal factors

Development ◽

10.1242/dev.122.2.439 ◽

1996 ◽

Vol 122 (2) ◽

pp. 439-447 ◽

Cited By ~ 14

Author(s):

G.K. Gittes ◽

P.E. Galante ◽

D. Hanahan ◽

W.J. Rutter ◽

H.T. Debase

Keyword(s):

Basement Membrane ◽

Adult Mouse ◽

Renal Capsule ◽

Pancreatic Development ◽

Embryonic Mouse ◽

Cell Lineages ◽

Ductal Cell ◽

Pancreatic Epithelium ◽

Embryonic Epithelium

Pancreatic organogenesis has been a classic example of epitheliomesenchymal interactions. The nature of this interaction, and the way in which endocrine, acinar and ductal cell lineages are generated from the embryonic foregut has not been determined. It has generally been thought that mesenchyme is necessary for all aspects of pancreatic development. In addition islets have been thought to derive, at least in part, from ducts. We microdissected 11-day embryonic mouse pancreas and developed several culture systems for assays of differentiation: (i) on transparent filters; (ii) suspended in a collagen I gel; (iii) suspended in a basement membrane rich gel; (iv) under the renal capsule of an adult mouse. Epithelia were grown either with or without mesenchyme, and then assayed histologically and immunohistochemically. Epithelium with its mesenchyme (growth systems i-iv) always grew into fully differentiated pancreas (acinar, endocrine, adn ductal elements). In the basement membrane-rich gel, epithelium without mesenchyme formed ductal structures. Under the renal capsule of the adult mouse the epithelium without mesenchyme exclusively formed clusters of mature islets. These latter results represent the first demonstration of pure islets grown from early pancreatic precursor cells. In addition, these islets seemed not to have originated from ducts. We propose that the default path for growth of embryonic pancreatic epithelium is to form islets. In the presence of basement membrane constituents, however, the pancreatic analage epithelium appears to be programmed to form ducts. Mesenchyme seems not to be required for all aspects of pancreatic development, but rather only for the formation of acinar structures. In addition, the islets seem to form from early embryonic epithelium (which only express non-acinar genes). This formation occurs without any specific embryonic signals, and without any clear duct or acinus formation.

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Abstract 218: Pericytic Laminin Regulates Blood-Brain Barrier Integrity in an Age-Dependent Manner

Stroke ◽

10.1161/str.48.suppl_1.218 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Yao Yao ◽

Jyoti Gautam ◽

Xuanming Zhang

Keyword(s):

Endothelial Cells ◽

Basement Membrane ◽

Blood Brain Barrier ◽

Vessel Density ◽

Brain Barrier ◽

Dependent Manner ◽

Vascular Integrity ◽

Blood Brain ◽

Age Dependent

Introduction: Laminin, a major component of the basement membrane, plays an important role in blood brain barrier (BBB) regulation. At the neurovascular unit, astrocytes, brain endothelial cells, and pericytes synthesize and deposit different laminin isoforms into the basement membrane. Previous studies from our laboratory showed that loss of astrocytic laminin induces age-dependent and region-specific BBB breakdown and intracerebral hemorrhage, suggesting a critical role of astrocytic laminin in vascular integrity maintenance. Laminin α4 (predominantly generated by endothelial cells) has been shown to regulate vascular integrity at embryonic/neonatal stage. The role of pericytic laminin in vascular integrity, however, remains elusive. Methods: We investigated the function of pericyte-derived laminin in vascular integrity using laminin conditional knockout mice. Specifically, laminin floxed mice were crossed with PDGFRβ-Cre line to generate mutants (PKO) with laminin deficiency in PDGFRβ + cells, which include both pericytes and vascular smooth muscle cells (vSMCs). To distinguish the contribution of pericyte- and vSMC-derived laminin, we also generated a vSMC-specific condition knockout line (TKO) by crossing the laminin floxed mice with Transgelin-Cre mice. In this study, mice of both genders on a C57Bl6 background were used. At least 5-6 animals were used in biochemical and histological analyses in this study. Results: Pericyte-derived laminin was abrogated in all PKO mice. However, only old but not young PKO mice showed signs of BBB breakdown and reduced vessel density, suggesting age-dependent changes. Consistent with these data, further mechanistic studies revealed reduced tight junction proteins, diminished AQP4 expression, and deceased pericyte coverage in old but not young PKO mice. In addition, neither BBB disruption nor decreased vessel density was observed in TKO mice, suggesting that these vascular defects are due to loss of pericyte- rather than vSMC-derived laminin. Conclusions: These results strongly suggest that pericyte-derived laminin active regulates BBB integrity and vessel density in an age-dependent manner. I would like this abstract to be considered for the Stroke Basic Science Award.

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