The length of the humerus was measured in 69 staged human embryos at developmental
stages 18-23 (7 and 8 weeks). It was found that the length of the
humerus increases from 2.0 mm at stage 18 to 5.4 mm at stage 23. There were
slight variations at certain of the stages investigated. Asymmetry between limb
lengths was not found during the embryonic period under examination

Bruska, M.

Woźniak, W.

English

Via Medica Journals

Folia Morphol. Vol. 65, No. 2, pp. 136–139Copyright © 2006 Via MedicaISSN 0015–5659www.fm.viamedica.plO R I G I N A L   A R T I C L E136Address for correspondence: Prof. W. Woźniak, Department of Anatomy, University School of Medical Sciences, Święcickiego 6, 60–781 Poznań,Poland, tel: +48 61 854 65 64, fax: + 48 61 854 65 68, e-mail: wwozniak@amp.edu.plThe length of the humerus in human embryosat developmental stages 18–23W. Woźniak, M. BruskaDepartment of Anatomy, University School of Medical Sciences, Poznań, Poland[Received 6 March 2006; Accepted 28 April 2006]The length of the humerus was measured in 69 staged human embryos at de-velopmental stages 18–23 (7 and 8 weeks). It was found that the length of thehumerus increases from 2.0 mm at stage 18 to 5.4 mm at stage 23. There wereslight variations at certain of the stages investigated. Asymmetry between limblengths was not found during the embryonic period under examination.Key words: human embryonic period, upper limb, humerus, metricfeaturesINTRODUCTIONThe first morphological evidence of the devel-oping limb is the swelling of the lateral body wallat pectoral and lumbar levels [9]. This swelling formsa limb bud, which is considered a morphogeneticfield and develops via a series of interactions of spe-cialised regions of the somatopleuric mesodermwith the overlying ectoderm. As the limb buds grow,four segments are progressively specified: 1) thegirdle (zonoskeleton), which includes the clavicleand scapula or hip bone, 2) the proximal segment(stylopodium), which forms a single skeletal element(the humerus/femur), 3) the medial segment (zy-gopodium), which has two skeletal elements (theradius-ulna/tibia-fibula) and 4) the distal segment(autopodium), containing the skeletal elements ofthe hand or foot.The growth and patterning of the limb bud isunder the control of limb organisers. The type oflimb bud and its patterning is specified before for-mation [23]. In each limb bud three signalling cen-tres have been identified, each operating mainly inone of the three orthogonal axes [3, 16]. These cen-tres are the apical ectodermal ridge (AER), the zoneof polarising activity (ZPA) and the non-AER ecto-derm [9].Apical ectodermal ridge is the ectoderm-form-ing longitudinal ridge of pseudostratified columnarcells. This ridge is an essential inductor in limb de-velopment and is required for elongation in the prox-imodistal axis. The function of the AER is mediatedby several members of the fibroblast growth factorfamily, which are synthesised by AER cells [22].In the formation of the variety of tissues thatcomprise the limb, such as the skeleton, muscula-ture, and vasculature, the Notch family signallingpathway is involved and is required for proper func-tioning of AER [12].Zone of polarising activity is a small group ofmesenchymal cells located at the posterior borderof the bud. These cells control the patterning in theanteroposterior (rostrocaudal) axis through theirproduction of sonic hedgehog (Shh). This regionalso specifies the positional identity of the digits.Patterning in the dorsoventral axis depends on thenon-AER ectoderm. The dorsal ectoderm expressesWnt7a, which induces expression of the homeoboxgene Lmx1, which is responsible for the dorsalisa-tion of mesoderm. The ventral ectoderm expressesEngrailed-1 (En-1), which controls ventral pattern-ing by restricting Wnt7a expression to the dorsalectoderm.137W. Woźniak et al., Upper limb in human embryosThe upper limb buds are present at stage 12(30 days) at the somitic levels s7-12. During stage 15(36 days) the hand plate appears. The bone of theupper limb develops at the end of embryonic period(stages 22–23).The prenatal development of the skeleton of thelimbs has been extensively studied [1, 14, 18, 19,21, 27–30, 32]. Most of these studies were concernedwith assessment of foetal maturity and have con-centrated on foetuses in utero near term [2, 10, 11,15, 17, 24, 25, 33]. The length of the developinghuman humerus has been studied in the foetal peri-od and was related to age rather than to crown-rump length [24, 25, 31].The present study was performed on staged hu-man embryos during the last two weeks of the em-bryonic period.MATERIAL AND METHODSA study was made of 69 embryos from the Col-lection of the Department of Anatomy of the Uni-versity School of Medical Sciences, Poznań and fromthe Collection of the Human Developmental Anato-my Center in Washington D.C. Embryos were stagedaccording to 23 developmental stages and age wasexpressed in postovulatory days. Investigated em-bryos were at developmental stages 18 to 23, andcrown-rump lengths ranged from 13 to 30.5 mm.Approximate ages of the embryos ranged from 44 to57 days.The majority of specimens were fixed in formalinand paraffin or paraplast were used for embedding.All embryos in which the humerus was measured weresectioned serially in the coronal or sagittal planes.Sections were stained with various techniques.Measurements were made under a low magnifi-cation light microscope with the aid of a microme-ter ocular and with the Leica Image Processing andAnalysis system.RESULTSIn embryos at the 7th week, stages 18, 19, and20, the skeletal elements of the arm, forearm andhand are in cartilage. The rounded head and thick-ened distal part of the humerus are discernible andthe longitudinal axes of the limbs are parallel. Dur-ing the 8th week (stages 21–23) the ossification pointappears in the shaft of the humerus [18, 26, 28–30].It was found that the humerus showed continuousgrowth during the last two weeks of the embryonicperiod. The length of the humerus increased from2.0 mm in stage 18 to 5.4 mm in stage 23 (Tables 1–6).Table 1. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 18No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 13.0 18 44 2.02 13.1 18 44 2.03 13.3 18 44 2.04 13.5 18 44 2.05 13.7 18 44 2.16 14.0 18 44 2.17 14.2 18 44 2.18 14.3 18 44 2.19 14.5 18 44 2.210 14.6 18 44 2.211 14.8 18 44 2.212 15.0 18 44 2.2Table 2. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 19No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 16.0 19 46 2.52 16.1 19 46 2.53 16.3 19 46 2.54 16.5 19 46 2.55 17.0 19 46 2.566 17.2 19 46 2.567 17.3 19 46 2.68 17.5 19 47 2.69 17.5 19 47 2.710 17.6 19 47 2.811 17.6 19 47 2.7At stage 18 the length of the humerus varied from2.0 mm to 2.2 mm (Table 1). In stage 19 the length ofthe humerus was between 2.5 mm and 2.7 mm (Ta-ble 2). Embryos at stage 20 have a length of the hu-merus between 2.9 mm and 3.2 mm (Table 3). In stage 21the length of the humerus varied from 3.4 mmto 3.5 mm (Table 4). At stage 22 the length of thehumerus was from 3.7 mm to 4.3 mm (Table 5) andat stage 23 this length varied from 4.3 mm to 5.4 mm(Table 6). It is evident that the humerus elongatesmarkedly during developmental stages 22 and 23 (theend of the embryonic period).138Folia Morphol., 2006, Vol. 65, No. 2The mean values for the investigated stages wereas follows: stage 18 — 2.1 mm, stage 19 — 2.6 mm,stage 20 — 3.0 mm, stage 21 — 3.4 mm, stage 22— 4.0 mm, stage 23 — 4.8 mm.DISCUSSIONThe skeleton tendons, and the sheaths of themuscles of the limbs are derived from the lateralplate mesenchyme, whereas the muscles of thelimbs are of somitic (myotomic) origin [18,27–30].Differential proximodistal growth of parts of thelimb bud result in two main changes: 1) the dorsalaspect of the limb grows faster than the ventral, andlater 2) the preaxial (rostral) border grows faster thanthe postaxial (caudal). These events cause the limbto curve around the body wall and form particularparts of the limb (shoulder, arm, forearm).Skeletal elements of the upper limb appear in themesenchyme during stages 13–16. Mesenchymal cellcondensation is a critical event in the initiation ofchondrogenesis and subsequent cartilage formation.Table 3. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 20No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 18.0 20 49 2.92 18.1 20 49 2.03 18.3 20 49 2.94 18.3 20 49 2.95 18.6 20 49 3.06 18.9 20 49 3.07 19.2 20 49 3.08 19.5 20 49 3.09 19.5 20 49 3.110 20.1 20 50 3.111 20.4 20 50 3.112 20.6 20 50 3.213 21.2 20 50 3.2Table 4. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 21No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 22.0 21 51 3.42 22.1 21 51 3.43 22.3 21 51 3.34 22.6 21 51 3.335 23.0 21 51 3.46 23.0 21 52 3.447 23.0 21 52 3.458 23.1 21 52 3.59 23.1 21 52 3.510 23.2 21 52 3.511 23.4 21 52 3.5Table 5. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 22No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 23.9 22 53 3.72 24.0 22 53 3.93 24.7 22 53 4.04 25.0 22 54 4.05 25.5 22 54 4.16 25.9 22 55 4.17 26.0 22 55 4.18 26.3 22 55 4.39 26.7 22 55 4.3Table 6. C-R length, developmental stage, age, and lengthof humerus in embryos at stage 23No. C-R length Developmental Age Length of[mm] stage [days] humerus [mm]1 27.9 23 56 4.32 28.1 23 56 4.53 28.3 23 56 4.54 28.5 23 56 4.65 28.7 23 56 4.66 28.7 23 56 4.77 29.1 23 56 4.98 29.5 23 56 5.09 29.9 23 57 5.010 30.0 23 57 5.111 30.2 23 57 5.212 30.3 23 57 5.113 30.5 23 57 5.4139W. Woźniak et al., Upper limb in human embryosHowever, the molecular mechanisms underlying the con-densation process itself remain largely unknown [20].One of the cell adhesion molecules implicated inthis process is N-cadherin. Displays a diffuse expres-sion pattern in the central core region in the pre-cartilaginous stage. In the development of particu-lar parts of the limb an important role play Hoxgenes [4–8, 13, 34].The humerus begins to chondrify before the ra-dius and the radius before the bones of the hand.Kelemen et al. [17] measured the long bones witha calliper and their results are not exact.The present study was made in staged embryos withprecisely determined ages. The humerus was measuredalong its long axis from exact proximal and distal points.There was no difference between male and femaleembryos in the length of the humerus. Such differencesappear later in foetal life [1]. Asymmetry between limblengths was not found in the examined embryos.REFERENCES1. Bagnal KM, Harris PF, Jones PRM (1982) A radiographicstudy of the longitudinal growth of primary ossifica-tion centers in limb long bones of the human fetus.Anat Rec, 203: 293–299.2. Brandfass R, Howhand W (1967) Determination of fe-tal weight by long-bone measurements. Obstet Gy-necol, 29: 230–234.3. 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The length of the humerus in human embryos at developmental stages 18-23

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The length of the humerus in human embryos at developmental stages 18-23

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