Lung Development

Abstract

Early respiratory development begins with the specification of the lung cell fate, followed by the emergence of lung buds from the ventral foregut endoderm. The respiratory tree is then elaborated through branching morphogenesis, and proliferation and differentiation of specialised cell types along the proximal–distal axis produces airways and alveoli, respectively. Lung development is orchestrated through crosstalk between the epithelium and the mesenchyme; morphogenesis and differentiation of the lung relies on diffusible signalling molecules that cross tissue layers to activate a complex network of transcription factors to drive development. Significant progress has been made in understanding the molecular regulation of lung morphogenesis through paracrine signalling pathways and transcription factors essential for lung development. Key Concepts Following specification of respiratory progenitor cells that are committed to the respiratory lineage, the lung buds emerge from the ventral foregut endoderm and subsequently elaborate the pulmonary tree through branching morphogenesis. Reciprocal interactions between the epithelium and the mesenchyme govern lung organogenesis and are mediated by diffusible factors. Critical signalling pathways known to be involved in lung development include Fgfs, Shh, Wnts, RA and TGF‐β superfamily. These factors are diffusible and act as means of communication and instruction between the tissue layers to drive development. The lung comprises specialised cell types that function to protect the lung, secrete surfactant or allow for gas exchange.

Endothelial cells are not required for specification of respiratory progenitors

“…The respiratory progenitors are identified by expression of the transcription factor Nkx2-1 , which is the earliest known marker of lung specification, along the ventral foregut endoderm. Following specification, lung morphogenesis ensues with the formation of two primary buds that evaginate into the surrounding splanchnic mesoderm at E9.5, followed by elaboration of the conducting airways through branching morphogenesis (Havrilak and Shannon, 2015a; Herriges and Morrisey, 2014; Metzger et al, 2008). …”

“…Events in early lung development are driven by reciprocal tissue interactions between the mesenchyme and the epithelium (Havrilak and Shannon, 2015a; Hines and Sun, 2014; McCulley et al, 2015; Shannon et al, 1998). These interactions are mediated by diffusible paracrine factors, and intensive research over the past two decades has identified many of the conserved signaling pathways governing early lung specification and morphogenesis.…”