Cheryll Tickle

University of Bath

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Lewis Wolpert

University College London

Alfonso Martínez Arias

Pompeu Fabra University

Peter A. Lawrence

NSF National Center for Atmospheric Research

David W. Burt

University of Edinburgh

Megan G. Davey

University of Edinburgh

Andrew Lumsden

King's College London

James Locke

University of Cambridge

Elizabeth J. Robertson

University of Oxford

Matthew Towers

University of Sheffield

James C. Smith

University College London

Cooperative Institutions

University College London

University of Dundee

University of Edinburgh

Washington University in St. Louis

University of Oxford

Wellcome Trust

Medical Research Council

University of Cambridge

Howard Hughes Medical Institute

Roslin Institute

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Fibroblast growth factors induce additional limb development from the flank of chick embryos

Cell (1995)

Martin J. Cohn Juan Carlos Izpisúa‐Belmonte Helen E. Abud John K. Heath Cheryll Tickle

Apical ectodermal ridge

Limb bud

Limb development

Mesenchyme

Flank

Polarity (international relations)

10.1016/0092-8674(95)90352-6

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Citations (581)

Cheryll Tickle to John Philip Trinkaus, 1969

Cheryll Tickle

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Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth

Development (2011)

Sung Won Cho Sungwook Kwak Thomas E. Woolley Min-Jung Lee Eun‐Jung Kim

Each vertebrate species displays specific tooth patterns in each quadrant of the jaw: the mouse has one incisor and three molars, which develop at precise locations and at different times. The reason why multiple teeth form in the jaw of vertebrates and the way in which they develop separately from each other have been extensively studied, but the genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of the key signaling molecules involved in the spatial patterning of teeth and other ectodermal organs such as hair, vibrissae and feathers. Sostdc1, a secreted inhibitor of the Wnt and Bmp pathways, also regulates the spatial patterning of teeth and hair. Here, by utilizing maternal transfer of 5E1 (an anti-Shh antibody) to mouse embryos through the placenta, we show that Sostdc1 is downstream of Shh signaling and suggest a Wnt-Shh-Sostdc1 negative feedback loop as a pivotal mechanism controlling the spatial patterning of teeth. Furthermore, we propose a new reaction-diffusion model in which Wnt, Shh and Sostdc1 act as the activator, mediator and inhibitor, respectively, and confirm that such interactions can generate the tooth pattern of a wild-type mouse and can explain the various tooth patterns produced experimentally.

GLI3

GLI1

FGF8

10.1242/dev.056051

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Citations (120)

Morphological Diversity: Taking the Spine out of Three-Spine Stickleback Dispatch

Cheryll Tickle Nicholas J. Cole

One of the most challenging problems in biology is to understand the basis for the marvellous morphological diversity of plants and animals. Three-spine stickleback come in a wide range of phenotypes with many anatomical variations [1,2]. Two recent papers have now reported the mapping of a major gene locus [3,4] that is associated with loss of pelvic spines and girdle — equivalent to loss of hindlimbs — and one of these papers [3] goes on to report the identification of a candidate gene in this locus. This gene, Pitx1, is already known from studies in chick and mouse embryos to play a crucial role in hindlimb development [5]. Sequence data [3] and gene expression studies [3,6] are consistent with the idea that a change in a regulatory region controlling Pitx1 expression in the developing pelvis is responsible for spine and girdle deficiency. Loss of pelvic structures has occurred, independently, in several natural populations of stickleback. Remarkably, these new data from Shapiro et al. [3] and Cresko et al. [4] implicate the same genetic locus in different populations. In fact, other aspects of stickleback anatomy are also now coming under the spotlight [4,7]. The flurry of publications on the genetics and embryology of three-spine stickleback has established this fish as a premier model for studying variation in vertebrates. The skeleton of three-spine stickleback, including pelvic spines and associated pelvic girdle, is reduced to varying extents in different populations [1]. Various explanations for the loss of spines have been suggested including lack of predator pressure and reduced levels of calcium. At one end of the spectrum are marine stickleback — very spiny fish, with a pair of pelvic spines articulating with a robust pelvic girdle (Figure 1A–C); at the other end, freshwater stickleback totally lacking pelvic spines and girdle (Figure 1D–G); and in between, a range of phenotypes showing varying degrees of pelvic reduction. Shapiro et al. [3] and Cresko et al. [4] crossed fully spined female stickleback with male stickleback completely lacking pelvic structures. Genetic mapping of offspring of both crosses located a single locus with a major influence on pelvic reduction. In order to identify candidate genes, Shapiro et al. [3] took note of the gene cascade involved in the initiation of hindlimb development that had been identified in chick and mouse embryos [5]. At least some of these genes are known to be conserved in paired fin development in zebrafish [8]. They then tested whether any of these genes map to the region responsible for pelvic reduction. Quite remarkably, the Pitx1 gene is located in this region and is tightly linked with pelvic reduction. Pitx1 was first identified in screens for novel homeodomain factors in mouse and human [9] and was called backfoot because it is expressed in hindlimbs but not forelimbs (Figure 2). Other genes encoding transcription factors of the Tbx family are also expressed in limb-type specific patterns, with Tbx4 specifically in hindlimbs, and the related gene Tbx5 specifically in forelimbs. Tbx4 appears to be downstream of Pitx1 [5] (Figure 2). An intriguing feature of hindlimbs of Pitx1-deficient mice is that they are frequently asymmetrical with right femur being shorter than left [10]. This characteristic resonates with the fact that stickleback pelvic reduction is also frequently asymmetrical, showing enhanced reduction on the right (Figure 1G), and indeed strengthens the candidacy of Pitx1. Asymmetry in hindlimb development in Pitx1-deficient mice has been ascribed to compensation by the related gene Pitx2, which is involved in establishing left–right asymmetry and is expressed preferentially on the left of early embryos (Figure 2). When the dosage of both Pitx genes is reduced in mice, the limbs are more severely affected [10]. The fact that Pitx gene dosage in mice leads to a range of different phenotypes fits with the varying degrees of pelvic reduction seen in stickleback populations. In stickleback, however, Pitx2 does not appear to be expressed in pelvic regions at the time girdle and spines are developing and thus seems unlikely to compensate for Pitx1 [6] (Figure 2). Shapiro et al. [3] sequenced Pitx1 in both spined and pelvic-reduced fish and found that the coding sequence is the same in fish of both phenotypes. Furthermore, although Pitx1 expression cannot be detected in the pelvic region of spineless fish (Figure 2), Pitx1 is expressed in other sites, such as thymus and lips, as it is in spined stickleback. One explanation is that different cis-regulatory elements govern Pitx1 expression in different anatomical sites and that pelvic reduction is due to a mutation in the element that drives Pitx1 expression specifically in this region. The simplicity of this model is attractive. It will be important to identify the predicted regulatory element and determine how it acts. One of the fascinating features of pelvic reduction is that the same anatomical change has evolved independently in different populations of stickleback — in Canada, Iceland, Alaska and Outer Hebrides. So is the genetic basis the same in these different fish? There are strong hints that the answer is yes. Shapiro et al. [3] and Cresko et al. [4] used pelvic-reduced fish from different locations for their crosses but nevertheless pinpointed the same major genetic locus. Classical genetic tests, crossing pelvic-reduced fish from different populations, Current Biology, Vol. 14, R422–R424, June 8, 2004, ©2004 Elsevier Ltd. All rights reserved. DOI 10.1016/j.cub.2004.05.034

Body plan

Pelvic girdle

Shoulder girdle

Axial skeleton

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Vertebrate development II: Xenopus and zebrafish

Oxford University Press eBooks (2019)

Lewis Wolpert Cheryll Tickle Alfonso Martínez Arias Peter A. Lawrence James Locke

This chapter discusses the earliest stages of vertebrate development by using Xenopus and zebrafish as model organisms. Moreover, it looks into how the embryo grows from fertilized eggs and develops with body axes and germ layers. The chapter also looks at the embryotic development in line with the relative roles of pre-existing maternal factors in the egg and its developmental program in the formation of body axes. In addition, the chapter explains the Spemann organizer alongside its role in patterning the body plan along the dorso-ventral and antero-posterior axes. The chapter acknowledges the similarity of body plan between Xenopus and zebrafish.

Body plan

10.1093/hesc/9780198800569.003.0004

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Plant development

Oxford University Press eBooks (2019)

Lewis Wolpert Cheryll Tickle Alfonso Martínez Arias Peter A. Lawrence James Locke

This chapter explores the development of plants. It expounds on how a plant’s architecture is the result of patterns of oriented cell divisions with a combination of positional signals and intercellular communication. Moreover, the chapter discusses cytoplasmic channels interconnecting plant cells. It notes the regeneration of an isolated somatic cell, the presence of relatively rigid walls, and the absence of any cell migration as distinctive features of plant development. The chapter discusses the early stages of plant development, in which involving both asymmetric cell division and cell-cell interactions are involved in line with patterning the body plan and the specificity of the shoot and root meristems., Twhile these meristems give rise to all the organs of the plant: stems, leaves, flowers, and roots.

Plant cell

Body plan

10.1093/hesc/9780198800569.003.0013

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Vertebrate limb development

Current Opinion in Genetics & Development (1995)

Cheryll Tickle

Apical ectodermal ridge

Limb development

Limb bud

Mesenchyme

10.1016/0959-437x(95)90052-i

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Citations (155)

The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development

Developmental Dynamics (2011)

Ian C. Dunn Ian R. Paton Allyson K. Clelland Sujith Sebastian Edward J. Johnson

Abstract Variable polydactylous phenotype of Silkie chicken feet, with expression of Shh in the developing limb buds (which is responsible for the polydactyly). From Dunn et al., Developmental Dynamics 240:1163–1172, 2011.

Polydactyly

Limb development

Ectopic expression

Variable Expression

GLI3

Limb bud

10.1002/dvdy.22645

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Citations (0)

Expression of the Connexin43 Gap Junctional Protein in Tissues at the Tip of the Chick Limb Bud Is Related to the EpitheliaI-Mesenchymal Interactions That Mediate Morphogenesis

Developmental Biology (1994)

Colin Green L. Bowles Angela M. Crawley Cheryll Tickle

Apical ectodermal ridge

Limb bud

Mesenchyme

Limb development

10.1006/dbio.1994.1002

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Citations (56)

Morphogens in chick limb development

BioEssays (1989)

P M Brickell Cheryll Tickle

Abstract Retinoic acid is a good candidate for a morphogen in chick limb bud development. The challenge now is to determine how retinoic acid interacts with limb bud cells and how the retinoic acid signal is integrated with other signals to mould and pattern the developing limb.

Morphogen

Limb bud

Limb development

10.1002/bies.950110508

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Citations (60)