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Here we delineate the ontogeny of the mammalian endoderm by generating 112,217 single-cell transcriptomes, which represent all endoderm populations within the mouse embryo until midgestation. We use graph-based approaches to model differentiating cells, which provides a spatio-temporal characterization of developmental trajectories and defines the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncover a relationship between descendants of these two lineages, in which epiblast cells differentiate into endoderm at two distinct time points--before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates and as they spatially converged within the nascent gut endoderm, which revealed these cells to be globally similar but retain aspects of their lineage history. We observed the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, which reflects their embryonic or extra-embryonic origin, and the coordinated patterning of these cells into organ-specific territories. The developing mouse gut endoderm, mapped at single-cell resolution, reveals trajectories of cell differentiation before and during gastrulation and the emergence of regionalized cell identities along the anterior-posterior axis of the gut tube., Author(s): Sonja Nowotschin [sup.1] , Manu Setty [sup.2] , Ying-Yi Kuo [sup.1] , Vincent Liu [sup.2] , Vidur Garg [sup.1] , Roshan Sharma [sup.2] , Claire S. Simon [sup.1] , [...]

This article, titled "Extended intersphincteric resection for low rectal cancer—A video vignette," demonstrates the laparoscopic technique of extended intersphincteric resection (ISR) for low rectal cancer. The video showcases the steps involved in the surgery, including finding the mesorectal excision plane, mobilizing the colon, performing pelvic dissection, and completing the perineal part of the procedure. The article also discusses the classification of ISR types, the definition of extended ISR, and the limited existing literature on the outcomes of extended ISR. The authors of the article include Varuna Sathyanarayan, Swapnil Patel, Sunny Jain, Vidur Garg, and Gurupreet Singh Gill. [Extracted from the article]

Cell fate decisions in early mammalian embryos are tightly regulated processes crucial for proper development. While FGF signaling plays key roles in early embryo patterning, its downstream effectors remain poorly understood. Our study demonstrates that the transcription factors Etv4 and Etv5 are critical mediators of FGF signaling in cell lineage specification and maturation in mouse embryos. We show that loss of Etv5 compromises primitive endoderm formation at pre-implantation stages. Furthermore, Etv4/5 deficiency delays naïve pluripotency exit and epiblast maturation, leading to elevated NANOG and reduced OTX2 expression within the blastocyst epiblast. As a consequence of delayed pluripotency progression, Etv4/5 deficient embryos exhibit anterior visceral endoderm migration defects post-implantation, a process essential for coordinated embryonic patterning and gastrulation initiation. Our results demonstrate the successive roles of these FGF signaling effectors in early lineage specification and embryonic body plan establishment, providing new insights into the molecular control of mammalian development., Competing Interests: Competing interests Authors declare that they have no competing interests.

Mouse genetic approaches when combined with live imaging tools are revolutionizing our current understanding of mammalian developmental biology. The availability and improvement of a wide variety of genetically encoded fluorescent proteins have provided indispensable tools to visualize cells and subcellular features in living organisms. It is now possible to generate genetically modified mouse lines expressing several spectrally distinct fluorescent proteins in a tissue-specific or -inducible manner. Such reporter-expressing lines make it possible to image dynamic cellular behaviors in the context of living embryos undergoing normal or aberrant development. As with all viviparous mammals, mouse embryos develop within the uterus, and so live imaging experiments require culture conditions that closely mimic the in vivo environment. Over the past decades, significant advances have been made in developing conditions for culturing both pre- and postimplantation-stage mouse embryos. In this chapter, we discuss routine methods for ex utero culture of preimplantation- and postimplantation-stage mouse embryos. In particular, we describe protocols for collecting mouse embryos of various stages, setting up culture conditions for their ex utero culture and imaging, and using laser scanning confocal microscopy to visualize live processes in mouse embryos expressing fluorescent reporters.