Abstract
The first cell lineage determination in embryos takes place when two cell populations are set apart, each differentiating into the trophectoderm (TE) and inner cell mass (ICM), respectively. It is widely believed that position/polarity cues play a key role in triggering this differentiation, but it remains unclear how extracellular cues are transduced into cell fate determination. Here, we provide evidence that supports that neogenin is implicated in relaying extracellular cues into the first cell fate determination in preimplantation mouse embryos. A polarized and transient distribution of neogenin was manifested in early blastomeres. Neogenin up-regulation by its overexpression accelerated ICM development in the blastocyst concomitant with the activation of the ICM-specific transcription factors Oct3/4, Sox2, and Nanog while its depletion by small hairpin RNAs (shRNAs) caused a developmental abnormality of poorly endowed ICM accompanied by the deactivation of Oct3/4, Sox2, and Nanog. Treatment with netrin-1 among neogenin ligands further impaired both embryonic development and ICM formation while repulsive guidance molecule c (RGMc) led to opposite consequences, enhancing ICM formation. From this study, we propose a model whereby neogenin interprets its own expression level to control the first cell fate determination in response to extracellular cues.
Highlights
Starting from fertilization and ending with implantation, preimplantation embryo development can be divided into several distinct stages: fertilization, cell cleavage, morula and blastocyst
Searching for a possible cellular receptor for polarity and/or positional cues implicated in early embryogenesis with a panel of antibodies, each of which recognizes an early signaling molecule involved in neurogenesis and neural path-finding, we fortuitously observed that neogenin, a member of cell-surface receptor proteins of the immunoglobulin superfamily [10], exhibited a polarized expression pattern within a single blastomere, raising an intriguing possibility that neogenin might play a role in early cell fate determination relaying extracellular stimuli
We identified two neogenin ligands, repulsive guidance molecule c (RGMc) and netrin-1, antagonistically act as potential modulators of the first cell fate specification
Summary
Starting from fertilization and ending with implantation, preimplantation embryo development can be divided into several distinct stages: fertilization, cell cleavage, morula and blastocyst. The establishment of polarity and positional allocation among blastomeres in the compaction and at subsequent stages (late morula stage) is a major determinant in initiating cell lineage differentiation into the trophectoderm (TE) and inner cell mass (ICM) in the blastocyst [1,2]. Two hypothetic models have been currently proposed to account for the mechanism of cell fate elaboration of the TE and ICM: The position model [3,4] and the cell polarity model [5]. The former proposes cell lineage determination is established largely by the position of blastomeres in the late morula, a stage at which inside and outside cells become distinct. Various lines of experimental evidence have supported the two models, ranging from cell division plane-dependent inheritance of polarity information to molecular components acting as positional cues [6,7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
