Expression of Patched 1 and insulin enhancer binding protein-1 in mouse embryonic foregut and early development of trachea-main bronchus

doi:10.16098/j.issn.0529-1356.2025.02.013

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (2) : 223-231. DOI: 10.16098/j.issn.0529-1356.2025.02.013

Histology and Embryology and Development Biology

Expression of Patched 1 and insulin enhancer binding protein-1 in mouse embryonic foregut and early development of trachea-main bronchus

YAN Yu-nan¹ SHI Liang^{1,2, 3*} LI Hui-chao⁴ CHEN Jun³ YAO Kai-ning¹ YANG Yan-ping^1,2*

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Abstract

Objective To explore the spatiotemporal expression patterns of Patched 1 (Ptch1) and insulin enhancer binding protein-1 (Isl1) in mouse embryonic foregut and their relationship with the early development of trachea-main bronchus. Methods The foregut of 60 mouse embryos at E9.5-12.5 was separated for the detection of Isl1 and sonic hedgehog (Shh) protein by Western blotting. Serial paraffin sections of 6 mouse embryos at E9.5-14.5 were taken for immunohistochemical staining and immunofluorescence double staining with Isl1, Ptch1, forkhead box protein A2 (Foxa2), type Ⅱ collagen α1 chain (Col2a1) and α-smooth muscle actin (α-SMA), as well as HE staining and Masson staining. Results The expression trend of Isl1 and Shh in foregut endoderm at E9.5-12.5 was similar, and the peak of Shh expression was later than Isl1. The foregut developed into the trachea at E9.5-12.5, Ptch1 was expressed in the thickening and protrusion of the respiratory endoderm, the laryngal-tracheal groove and the solid cell cord, accompanied by the increase and aggregation of Isl1-positive mesenchymal cells, forming a characteristic pyramidal structure centered on the respiratory endoderm and the solid cell cord; The main bronchus appeared at E12.5-13.5, Ptch1 was only expressed in its lateral wall, accompanied by the accumulation of Isl1-positive mesenchymal cells; The trachea-main bronchial epithelium lost Ptch1 expression and the surrounding Isl1-positive mesenchymal cells also decreased rapidly at E13.5-14.5.Col2a1-positive chondrocytes first appeared in the Isl1-positive mesenchymal area adjacent to the Ptch1-positive epithelium at E12.5; Col2a1-positive cartilage was nested within the Isl1-positive mesenchymic area in a “C” shape and expanded in a proximal-distal pattern at E12.5-13.5; Col2a1-positive cartilage extended to the dorsal trachea beyond the Isl1-positive mesenchyma and encircles α-SMA positive smooth muscle in a circular manner at E14.5. Conclusion The expression of Ptch1 in the foregut endoderm is involved in the development and morphogenesis of the trachea-main bronchus epithelium, and is closely related to the proliferation and aggregation of Isl1-positive mesenchyme in the trachea-main bronchial wall, Subsequently, they jointly determine the time, location and extent of airway cartilage.

Key words

Patched 1 / Insulin enhancer binding protein-1 / Respiratory endoderm / Mesenchyme / Cartilage / Immunohistochemistry / Immunofluorescence / Mouse embryo

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YAN Yu-nan SHI Liang LI Hui-chao CHEN Jun YAO Kai-ning YANG Yan-ping. Expression of Patched 1 and insulin enhancer binding protein-1 in mouse embryonic foregut and early development of trachea-main bronchus[J]. Acta Anatomica Sinica. 2025, 56(2): 223-231 https://doi.org/10.16098/j.issn.0529-1356.2025.02.013

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