Table 2.

Selected mesenchymal intracellular signaling pathways involved in pancreas development

Signaling pathway	SOA in pancreatic mesenchyme	SOA* in pancreatic epithelium	Function (in pancreas)	LOF (in pancreas)	Referencess
BMP	E9.5-E12.5	ND	• Normal development of mesenchyme • Regulation of cellular composition	• Production of endocrines concomitant to exocrine decrease • Severe hypoplasia • Reduced epithelial branching • Anterior extension of dorsal pancreas into stomach mesenchyme • Vascular remodeling	[217]
RA	~ E11	E11	• Exocrine lineage selection • Up-regulation of mesenchymal laminin-1 • Ductal differentiation • Generation of Ngn3+ and β-cells	• Production of acinar cells in favor of ductal cells	[218–220]
Wnt	~ E13	E13.5	• Expansion/differentiation of epithelial progenitors • Regulation of organ growth • Survival/expansion of mesenchyme	• Reduced PP proliferation and hypoplasia • Decrease in endocrine progenitor and islet cell mass • Reduced β-, PP-, and delta- cells but not alpha-cells	[221, 222]
SHH	≥ E13	≤ 2nd transition	• Regulation of alpha and β-cell growth rate • Fine-tuning for proper development/organogenesis	• Severe agenesis in onset of development# • Reduced endocrine and exocrine area • Disrupted islet morphology and cellular composition at E14.5#	[223–227]

LOF results of loss of function, SOA stage of activation, ND no data provided

^*This table displays the signaling pathways activated intracellularly in the mesenchyme compartment while this column shows the time of activation of these signaling pathways in the epithelium compartment

^#While this column displays the effects of LOF of SHH, these items are caused by its gain of function!