Mutations in the Katnb1 gene cause left-right asymmetry and heart defects.

BACKGROUND: The microtubule-severing protein complex katanin is composed two subunits, the ATPase subunit, KATNA1, and the noncatalytic regulatory subunit, KATNB1. Recently, the Katnb1 gene has been linked to infertility, regulation of centriole and cilia formation in fish and mammals, as well as neocortical brain development. KATNB1 protein is expressed in germ cells in humans and mouse, mitotic/meiotic spindles and cilia, although the full expression pattern of the Katnb1 gene has not been described. RESULTS: Using a knockin-knockout mouse model of Katnb1 dysfunction we demonstrate that Katnb1 is ubiquitously expressed during embryonic development, although a stronger expression is seen in the crown cells of the gastrulation organizer, the murine node. Furthermore, null and hypomorphic Katnb1 gene mutations show a novel correlation between Katnb1 dysregulation and the development of impaired left-right signaling, including cardiac malformations. CONCLUSIONS: Katanin function is a critical regulator of heart development in mice. These findings are potentially relevant to human cardiac development. Developmental Dynamics 246:1027-1035, 2017. © 2017 Wiley Periodicals, Inc.

KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

An essential role for katanin p80 and microtubule severing in male gamete production.

Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development.

Get SET: aligning anatomy demonstrator programmes with Surgical Education and Training selection criteria.

BACKGROUND: Prevocational doctors aspiring to surgical careers are commonly recruited as anatomy demonstrators for undergraduate and graduate medical programmes. Entry into Surgical Education and Training (SET) is highly competitive and a unique opportunity exists to align anatomy demonstrator programmes with the selection criteria and core competencies of SET programmes. This study used a qualitative approach to (i) determine what criteria applicants for SET are assessed on and (ii) identify criteria that could be aligned with and enhanced by an anatomy demonstrator programme. METHODS: The selection guidelines of all nine surgical specialties for the 2017 intake of SET trainees were analysed using qualitative content analysis methodology. RESULTS: The Royal Australasian College of Surgeons adopted a holistic approach to trainee selection that assessed both discipline-specific and discipline-independent skills. Qualitative content analysis identified eight categories of key selection criteria: medical expertise, scholarly activity, professional identity, interpersonal skills, integrity, self-management, insight and self-awareness and community involvement. The structured curriculum vitae was heavily weighted towards discipline-specific skills, such as medical expertise and scholarly activity. Insufficient information was available to determine the weighting of selection criteria assessed by the structured referee reports or interviews. CONCLUSION: Anatomy demonstrator programmes provide prevocational doctors with unique opportunities to develop surgical skills and competencies in a non-clinical setting. Constructively aligned anatomy demonstrator programmes may be particularly beneficial for prevocational doctors seeking to improve their anatomical knowledge, teaching skills or scholarly activity.

Dissecting the role of sessional anatomy teachers: A systematic literature review.

Worldwide there is a growing reliance on sessional teachers in universities. This has impacted all disciplines in higher education including medical anatomy programs. The objective of this review was to define the role and support needs of sessional anatomy teachers by reporting on the (1) qualifications, (2) teaching role, (3) training, and (4) performance management of this group of educators. A systematic literature search was conducted on the 27 July 2017 in Scopus, Web of Science, and several databases on the Ovid, ProQuest and EBSCOhost platforms. The search retrieved 5,658 articles, with 39 deemed eligible for inclusion. The qualifications and educational distance between sessional anatomy teachers and their students varied widely. Reports of cross-level, near-peer and reciprocal-peer teaching were identified, with most institutes utilizing recent medical graduates or medical students as sessional teachers. Sessional anatomy teachers were engaged in the full spectrum of teaching-related duties from assisting students with cadaveric dissection, to marking student assessments and developing course materials. Fourteen institutes reported that training was provided to sessional anatomy teachers, but the specific content, objectives, methods and effectiveness of the training programs were rarely defined. Evaluations of sessional anatomy teacher performance primarily relied on subjective feedback measures such as student surveys (n = 18) or teacher self-assessment (n = 3). The results of this systematic review highlight the need for rigorous explorations of the use of sessional anatomy teachers in medical education, and the development of evidence-based policies and training programs that regulate and support the use of sessional teachers in higher education. Anat Sci Educ 11: 410-426. © 2017 American Association of Anatomists.